PLA2G6 SNPs与PD发病风险的相关性研究及PLA2G6酶活性下降导致细胞凋亡的研究
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摘要
研究背景：帕金森病(Parkinson's disease, PD)又称震颤麻痹(Paralysis agitans),是发病率仅次于阿尔兹海默病的第二大神经退行性疾病。近年来,人们发现基因单核苷酸多态性(single nucleotide polymorphism,SNP)与PD具有相关性,且基因SNPs在群体中的分布具有明显的种族特异性。PLA2G6基因,也被称作PARK14,是2009年Paisan-Ruiz等在一个常染色体隐性遗传性早发性帕金森综合征家系中发现的,但是近年来关于PLA2G6基因的SNPs与PD发病风险是否具有相关性尚无文献报道。研究目的：本研究旨在探讨四个PLA2G6的SNPs与华中地区汉族人群散发性PD是否具有相关性。研究方法：此部分实验主要采用了DNA直接测序的方法,检测了中国华中地区汉族人群531例散发性帕金森病患者和561例健康对照者的PLA2G6基因的四个SNPs:rs4375、 rs2267369、rs132985和rs2284063。实验结果：1. PLA2G6基因rs4375、rs2267369、rs132985、rs2284063在中国华中地区汉族人群中是常见的单核苷酸多态位点,不支持这四个SNPs是帕金森病的危险因素。2.将散发性PD组和正常对照组分为≤50岁人群、>50岁人群两组进行分析,结果发现PLA2G6基因rs4375、rs2267369、 rs132985、rs2284063在无论基因型还是等位基因分析均无统计学差别。3.对SNPs进行性别分层后分析发现：男性PD病人与男性正常对照组之间rs132985在基因型和等位基因方面分析都具有明显统计学意义,而两组人群根据性别进行分层后分析发现rs4375、 rs2267369、rs2284063的基因型和等位基因均无统计学差别。4.单体型rs132985A-rs2284063C在散发性PD组和正常对照组之间具有统计学意义,而其余单体型在散发性PD组和正常对照组之间均无统计学意义。结论：PLA2G6基因并不是中国汉族人群PD发病的风险基因。
研究背景：PLA2G6基因位于22q13.1,其编码的蛋白质称为iPLA2VIA或iPLA2β,此基因导致PD的发病机制尚无报道。iPLA2β是磷脂酶A2(PLA2)的一种,对于维持膜的流动性具有重要的作用。研究目的：本部分实验主要研究iPLA2β酶活性下降是否通过损伤线粒体而导致细胞凋亡的发生。研究方法：本部分主要运用了MTT实验、流式细胞术,电镜观察、Western Blots实验等检测了与线粒体及细胞凋亡相关的指标。实验结果：1.MTT实验发现不同浓度S-BEL预孵育SH-SY5Y细胞可导致细胞活性出现不同程度的下降。2.运用流式细胞仪检测发现不同浓度S-BEL预孵育SH-SY5Y细胞可以导致线粒体膜电位下降。3.运用电镜检测发现不同浓度S-BEL预孵育SH-SY5Y细胞可以导致线粒体形态发生改变及细胞核固缩等改变。4. Western Blots检测发现不同浓度S-BEL预孵育细胞可以导致SH-SY5Y细胞线粒体细胞色素C释放入细胞浆内。5.Western Blots检测发现不同浓度S-BEL预孵育细胞可以导致SH-SY5Y细胞caspase9、caspase3活化。6.运用Annexin-PI检测发现不同浓度S-BEL预孵育细胞均可以导致SH-SY5Y细胞发生细胞凋亡。结论：iPLA2β酶活性下降可以通过线粒体途径导致细胞凋亡。当然本部分实验仅是细胞水平的研究,进一步的动物模型仍在构建中。
研究背景：PLA2G6基因突变可导致婴儿神经轴索变性病(INAD,infantile neuroaxonal dystrophy)及常染色体隐性遗传性PD,因为部分INAD病人和常染色体隐性遗传性早发性帕金森综合征患者在MRI上脑内苍白球区域可见铁离子沉积,因此也被称作脑内铁离子沉积性疾病-2型(Neurodegenerative disorders with brain iron accumulation,NBIA-2)。散发性PD病人脑内黑质(SN)区域的铁水平增高已被证实,且已被证明为散发性PD的重要发病原因之一。铁离子增高可以导致细胞内活性氧水平增高、加重线粒体的损伤从而导致细胞凋亡的发生。研究目的：本部分主要研究iPLA2β酶活性下降是否会导致铁离子沉积、铁离子代谢障碍从而导致细胞凋亡。研究方法：本部分主要运用Perls铁染色方法观察是否存在铁离子沉积、运用Western Blots方法观察铁离子代谢相关蛋白的变化。研究结果：1.运用Perls铁染色方法发现不同浓度S-BEL孵育SH-SY5Y细胞并不能导致细胞内铁离子沉积。2.对SH-SY5Y细胞预孵育铁离子螯合剂去铁敏,并不能降低S-BEL孵育所导致的caspase3活化带的表达。3.不同浓度S-BEL孵育SH-SY5Y细胞并不能导致铁离子转运相关蛋白的表达调控发生障碍。4.不同浓度S-BEL孵育Neuro2a细胞并不能导致细胞内铁离子沉积。5.对Neuro2a细胞预孵育铁离子螯合剂去铁敏,并不能改变S-BEL孵育所导致的细胞存活率下降。6.运用不同浓度S-BEL孵育Neuro2a细胞发现铁离子代谢相关蛋白的表达变化未出现障碍。结论：iPLA2β酶活性下降不能通过导致铁离子沉积途径导致细胞凋亡的发生。当然本部分实验仅是细胞水平的研究,进一步的动物模型仍在构建中。
Background:Parkinson's disease (PD), also known as paralysis agitans, is one of the most common neurodegenerative diseases. In recent years, the relationship between single nucleotide polymorphisms (SNP) and the risk of Parkinson's disease becomes a central issue, and the single nucleotide polymorphisms in the population distribution have obvious racial specificity. The PLA2G6gene, also called PARK14, was found in2009when Paisan-Ruiz et al studying the autosomal recessive hereditary PD pedigrees, but until now there is still no study about the PLA2G6gene single nucleotide polymorphisms and the risk of PD. Objective:This part of study aims at exploring the relationship between the four of selected PLA2G6single nucleotide polymorphic loci and sporadic Parkinson's disease. Methods:In this study, direct DNA sequencing methods were used to detect the531patients with sporadic Parkinson's disease and561healthy people of Han population, four SNPs of PLA2G6gene were selected:rs4375, rs2267369, rs132985and rs2284063. Results:The results of the association study of4tag SNPs in Chinese PD patients and unrelated controls are as follows:1. The SNPs (rs4375, rs2267369, rs132985, rs2284063) are common single nucleotide polymorphic loci in Han population in China, which are not risk factors of Parkinson's disease.2. Genotype and allele frequencies of all SNPs in patients with either early-onset (EOPD,≤50years) or late-onset (>50years) PD revealed no statistically significant differences from controls.3. The rs132985allele frequency showed a difference in male patients but not in female patients after adjustment for age; Genotype and allele frequencies of rs4375、rs2267369、rs2284063in patients with either male or female PD revealed no statistically significant differences from controls.4. The haplotype rs132985A—2284063C was associated with the increased risk of developing PD in our case control sample set. Conclusion:The results showed that the four single nucleotide polymorphic loci selected were common in Chinese Han population and were not the risk factors in Parkinson's disease.
Background:The PLA2G6gene located at22q13.1, encodes a protein called iPLA2VIA or iPLA2β, there is still no paper reported about this gene in the pathogenesis of Parkinson's. IPLA2β is one of the phospholipase A2(PLA2), which plays an important role in maintaining the membrane fluidity. Objective:This part aimed at study the relationship between the reduction of iPLA2βactivity and apoptosis. Methods:The specific inhibitor S-BEL was used to pre-incubate SH-SY5Y cells, the activity of iPLA2β enzyme was detected, and MTT, Western Blots, transmission electronic microscopy, Flow Cytometry were used to detect the indicators of related mitochondrial and apoptosis. Results:1. Different concentrations of S-BEL pre-incubation can lead to the decrease of SH-SY5Y cells activity.2. Different concentrations of S-BEL pre-incubation of SH-SY5Y cells can lead to decline in mitochondrial membrane potential.3. Different concentrations of S-BEL pre-incubation can result in cytochrome C release from mitochondrial into the cytoplasm in SH-SY5Y cells.4. Different concentrations of S-BEL pre-incubation can result in caspase9, caspase3activation in SH-SY5Y cells.5. Different concentrations of S-BEL pre-incubation can result in SH-SY5Y cell apoptosis using Annexin-PI detection. Conclusion:The decrease of iPLA2(3activity may cause mitochondrial dysfunction which leads to apoptosis. Of course, our experiments were done on the cellular level and animal model is on the agenda.
Background:The mutation of PLA2G6gene can lead to infantile neuroaxonal dystrophy (INAD) and autosomal recessive genetic PD, because in the globus pallidus region of part of the INAD and autosomal recessive PD patients there were MRI visible iron deposition, and therefore the disease of the mutation of PLA2G6gene is classified as the brain iron deposition disease—2(neurodegenerative disorders with brain iron accumulation, NBIA—2). In sporadic patients of Parkinson's disease, the iron levels have been confirmed to be increased in substantia nigra (SN), and the increased iron proved to be one of the important causes of Parkinson's disease. Objective:Whether the decrease of the iPLA2β activity may cause the disturbance of iron metabolism then leading to apoptosis become the third part of our study. Methods:This section used Perls iron staining; Western Blots to observe whether there are changes in the deposition of iron and iron metabolism related proteins. Results:The results are as follows:1. There was no intracellular iron deposition in SH-SY5Y cells incubated with different concentrations of S-BEL.2. SH-SY5Y cells were pre-incubated iron chelator deferoxamine, but the protein level of caspase3caused by S-BEL incubation can not be reduced.3. There was no disorder for the expression of iron transport protein for SH-SY5Y cells.4. There was no intracellular iron deposition in Neuro2a cells incubated with different concentrations of S-BEL.5. Neuro2a cells were pre-incubated iron chelator deferoxamine, but cells activity caused by S-BEL incubation can not be rescued.6. There was no disorder for the expression of iron transport protein for Neuro2a cells. Conclusion:The decrease of iPLA2P activity may not cause iron deposition. Of course, our experiments were done on the cellular level and animal model is on the agenda.
研究背景：PLA2G6基因位于22q13.1,其编码的蛋白质称为iPLA2VIA或iPLA2β,此基因导致PD的发病机制尚无报道。iPLA2β是磷脂酶A2(PLA2)的一种,对于维持膜的流动性具有重要的作用。研究目的：本部分实验主要研究iPLA2β酶活性下降是否通过损伤线粒体而导致细胞凋亡的发生。研究方法：本部分主要运用了MTT实验、流式细胞术,电镜观察、Western Blots实验等检测了与线粒体及细胞凋亡相关的指标。实验结果：1.MTT实验发现不同浓度S-BEL预孵育SH-SY5Y细胞可导致细胞活性出现不同程度的下降。2.运用流式细胞仪检测发现不同浓度S-BEL预孵育SH-SY5Y细胞可以导致线粒体膜电位下降。3.运用电镜检测发现不同浓度S-BEL预孵育SH-SY5Y细胞可以导致线粒体形态发生改变及细胞核固缩等改变。4. Western Blots检测发现不同浓度S-BEL预孵育细胞可以导致SH-SY5Y细胞线粒体细胞色素C释放入细胞浆内。5.Western Blots检测发现不同浓度S-BEL预孵育细胞可以导致SH-SY5Y细胞caspase9、caspase3活化。6.运用Annexin-PI检测发现不同浓度S-BEL预孵育细胞均可以导致SH-SY5Y细胞发生细胞凋亡。结论：iPLA2β酶活性下降可以通过线粒体途径导致细胞凋亡。当然本部分实验仅是细胞水平的研究,进一步的动物模型仍在构建中。
研究背景：PLA2G6基因突变可导致婴儿神经轴索变性病(INAD,infantile neuroaxonal dystrophy)及常染色体隐性遗传性PD,因为部分INAD病人和常染色体隐性遗传性早发性帕金森综合征患者在MRI上脑内苍白球区域可见铁离子沉积,因此也被称作脑内铁离子沉积性疾病-2型(Neurodegenerative disorders with brain iron accumulation,NBIA-2)。散发性PD病人脑内黑质(SN)区域的铁水平增高已被证实,且已被证明为散发性PD的重要发病原因之一。铁离子增高可以导致细胞内活性氧水平增高、加重线粒体的损伤从而导致细胞凋亡的发生。研究目的：本部分主要研究iPLA2β酶活性下降是否会导致铁离子沉积、铁离子代谢障碍从而导致细胞凋亡。研究方法：本部分主要运用Perls铁染色方法观察是否存在铁离子沉积、运用Western Blots方法观察铁离子代谢相关蛋白的变化。研究结果：1.运用Perls铁染色方法发现不同浓度S-BEL孵育SH-SY5Y细胞并不能导致细胞内铁离子沉积。2.对SH-SY5Y细胞预孵育铁离子螯合剂去铁敏,并不能降低S-BEL孵育所导致的caspase3活化带的表达。3.不同浓度S-BEL孵育SH-SY5Y细胞并不能导致铁离子转运相关蛋白的表达调控发生障碍。4.不同浓度S-BEL孵育Neuro2a细胞并不能导致细胞内铁离子沉积。5.对Neuro2a细胞预孵育铁离子螯合剂去铁敏,并不能改变S-BEL孵育所导致的细胞存活率下降。6.运用不同浓度S-BEL孵育Neuro2a细胞发现铁离子代谢相关蛋白的表达变化未出现障碍。结论：iPLA2β酶活性下降不能通过导致铁离子沉积途径导致细胞凋亡的发生。当然本部分实验仅是细胞水平的研究,进一步的动物模型仍在构建中。
Background:Parkinson's disease (PD), also known as paralysis agitans, is one of the most common neurodegenerative diseases. In recent years, the relationship between single nucleotide polymorphisms (SNP) and the risk of Parkinson's disease becomes a central issue, and the single nucleotide polymorphisms in the population distribution have obvious racial specificity. The PLA2G6gene, also called PARK14, was found in2009when Paisan-Ruiz et al studying the autosomal recessive hereditary PD pedigrees, but until now there is still no study about the PLA2G6gene single nucleotide polymorphisms and the risk of PD. Objective:This part of study aims at exploring the relationship between the four of selected PLA2G6single nucleotide polymorphic loci and sporadic Parkinson's disease. Methods:In this study, direct DNA sequencing methods were used to detect the531patients with sporadic Parkinson's disease and561healthy people of Han population, four SNPs of PLA2G6gene were selected:rs4375, rs2267369, rs132985and rs2284063. Results:The results of the association study of4tag SNPs in Chinese PD patients and unrelated controls are as follows:1. The SNPs (rs4375, rs2267369, rs132985, rs2284063) are common single nucleotide polymorphic loci in Han population in China, which are not risk factors of Parkinson's disease.2. Genotype and allele frequencies of all SNPs in patients with either early-onset (EOPD,≤50years) or late-onset (>50years) PD revealed no statistically significant differences from controls.3. The rs132985allele frequency showed a difference in male patients but not in female patients after adjustment for age; Genotype and allele frequencies of rs4375、rs2267369、rs2284063in patients with either male or female PD revealed no statistically significant differences from controls.4. The haplotype rs132985A—2284063C was associated with the increased risk of developing PD in our case control sample set. Conclusion:The results showed that the four single nucleotide polymorphic loci selected were common in Chinese Han population and were not the risk factors in Parkinson's disease.
Background:The PLA2G6gene located at22q13.1, encodes a protein called iPLA2VIA or iPLA2β, there is still no paper reported about this gene in the pathogenesis of Parkinson's. IPLA2β is one of the phospholipase A2(PLA2), which plays an important role in maintaining the membrane fluidity. Objective:This part aimed at study the relationship between the reduction of iPLA2βactivity and apoptosis. Methods:The specific inhibitor S-BEL was used to pre-incubate SH-SY5Y cells, the activity of iPLA2β enzyme was detected, and MTT, Western Blots, transmission electronic microscopy, Flow Cytometry were used to detect the indicators of related mitochondrial and apoptosis. Results:1. Different concentrations of S-BEL pre-incubation can lead to the decrease of SH-SY5Y cells activity.2. Different concentrations of S-BEL pre-incubation of SH-SY5Y cells can lead to decline in mitochondrial membrane potential.3. Different concentrations of S-BEL pre-incubation can result in cytochrome C release from mitochondrial into the cytoplasm in SH-SY5Y cells.4. Different concentrations of S-BEL pre-incubation can result in caspase9, caspase3activation in SH-SY5Y cells.5. Different concentrations of S-BEL pre-incubation can result in SH-SY5Y cell apoptosis using Annexin-PI detection. Conclusion:The decrease of iPLA2(3activity may cause mitochondrial dysfunction which leads to apoptosis. Of course, our experiments were done on the cellular level and animal model is on the agenda.
Background:The mutation of PLA2G6gene can lead to infantile neuroaxonal dystrophy (INAD) and autosomal recessive genetic PD, because in the globus pallidus region of part of the INAD and autosomal recessive PD patients there were MRI visible iron deposition, and therefore the disease of the mutation of PLA2G6gene is classified as the brain iron deposition disease—2(neurodegenerative disorders with brain iron accumulation, NBIA—2). In sporadic patients of Parkinson's disease, the iron levels have been confirmed to be increased in substantia nigra (SN), and the increased iron proved to be one of the important causes of Parkinson's disease. Objective:Whether the decrease of the iPLA2β activity may cause the disturbance of iron metabolism then leading to apoptosis become the third part of our study. Methods:This section used Perls iron staining; Western Blots to observe whether there are changes in the deposition of iron and iron metabolism related proteins. Results:The results are as follows:1. There was no intracellular iron deposition in SH-SY5Y cells incubated with different concentrations of S-BEL.2. SH-SY5Y cells were pre-incubated iron chelator deferoxamine, but the protein level of caspase3caused by S-BEL incubation can not be reduced.3. There was no disorder for the expression of iron transport protein for SH-SY5Y cells.4. There was no intracellular iron deposition in Neuro2a cells incubated with different concentrations of S-BEL.5. Neuro2a cells were pre-incubated iron chelator deferoxamine, but cells activity caused by S-BEL incubation can not be rescued.6. There was no disorder for the expression of iron transport protein for Neuro2a cells. Conclusion:The decrease of iPLA2P activity may not cause iron deposition. Of course, our experiments were done on the cellular level and animal model is on the agenda.
引文
[1]Zhang ZX, Roman GC, Hong Z et. Parkinson's disease in China: prevalence in Beijing, Xian, and Shanghai. Lancet,2005,365(9459):595-597.
[2]Lv Z, Guo J, Sun Q et al. Association between PLA2G6 gene polymorphisms and Parkinson's disease in the Chinese Han population. Parkinsonism Relat Disord,2012,18(5):641-644.
[3]Singleton AB, Farrer M, Johnson J, et al.alpha-Synuclein locus triplication causes Parkinson's disease. Science,2003,302(5646):841
[4]Kitada T, Asakawa S, Hattori N, et al.Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature,1998,392(6676):605-608
[5]Leroy E, Boyer R, Auburger G, et al.The ubiquitin pathway in Parkinson's disease. Nature,1998,395(6701):451-452
[6]Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science,2004,304(5674): 1158-1160
[7]Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science,2003,299(5604):256-259
[8]Zimprich A, Biskup S, Leitner P, et al.Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron,2004, 44(4):601-607
[9]Ramirez A, Heimbach A, Grundemann J, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet,2006,38(10):1184-1191
[10]Lautier C, Goldwurm S, Diirr A, et al. Mutations in the GIGYF2 (TNRC15) gene at the PARK11 locus in familial Parkinson disease.Mutations in the GIGYF2 (TNRC15) gene at the PARK11 locus in familial Parkinson disease. Am J Hum Genet,2008,82(4):822-833
[11]Strauss KM, Martins LM, Plun-Favreau H, et al. Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum Mol Genet, 2005,14(15):2099-2111
[12]Paisan-Ruiz C, Bhatia KP, Li A, et al.Characterization of PLA2G6 as a Locus for Dystonia-Parkinsonism. Annals of Neurology,2009,65(1):19-23.
[13]Di Fonzo A, Dekker MC, Montagna P, et al. FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology, 2009,72(3):240-245
[14]Hsu LJ, Sagara Y, Arroyo A, et al. alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol,2000,157(2):401-410
[15]Volles MJ, Lee SJ, Rochet JC, et al. Vesicle permeabilization by protofibrillar alpha-synuclein:implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry,2001,40(26):7812-7819
[16]Shi CH, Tang BS, Wang L, et al. PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort. Neurology, 2011,77(1):75-81.
[17]Gregory A, Kurian MA, Maher ER, Hogarth P, Hayflick SJ. PLA2G6-Associated Neurodegeneration. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2008 Jun 19 [updated 2012 Apr 19
[18]Gregory A, Westaway SK, Holm IE, et al. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology,2008,71(18):1402-1409.
[19]Lv Z, Jiang H, Xu H et al. Increased iron levels correlate with the selective nigral dopaminergic neuron degeneration in Parkinson's disease. J Neural Transm,2011,118(3):361-369.
[20]Paisan-Ruiz C, Li A, Schneider SA, Holton JL, et al. Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. Neurobiol Aging,2012,33(4):814-823.
[21]Kauther KM, Hoft C, Rissling I, et al. The PLA2G6 gene in early-onset Parkinson's disease. Mov Disord,2011,26(3):2415-2417.
[22]Falchi M, Bataille V, Hayward NK et al. Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. Nat Genet,2009,41(8):915 919.
[23]Liu R, Gao X, Lu Y et al. Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology,2011,76(23):2002-2009.
[24]Bertoni JM, Arlette JP, Fernandez HH, et al. North American Parkinson's and Melanoma Survey Investigators. Increased melanoma risk in Parkinson disease: a prospective clinicopathological study. Arch Neurol,2010,67(3):347-352.
[25]Baade PD, Fritschi L, Freedman DM. Mortality due to amyotrophic lateral sclerosis and Parkinson's disease among melanoma patients. Neuroepidemiology,2007,28(3):16-20.
[26]Gao X, Simon KC, Han J, et al. Family history of melanoma and Parkinson disease risk. Neurology,2009,73(1):1286-1291.
[27]Skibba JL, Pinckley J, Gilbert EF, et al. Multiple primary melanoma following administration of levodopa. Arch Pathol,1972,93(3):556-561.
[28]Fiala KH, Whetteckey J, Manyam BV. Malignant melanoma and levodopa in Parkinson's disease:causality or coincidence? Parkinsonism Relat Disord, 2003,9(1):321-327.
[29]Millikin D, Meese E, Vogelstein B, et al. Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma. Cancer Res, 1991,51(6):5449-5453.
[30]Fasano M, Giraudo S, Coha S, et al. Residual substantia nigra neuromelanin in Parkinson's disease is cross-linked to alpha-synuclein. Neurochem Int, 2003,42(3):603-606.
[31]Paisn-Ruiz C, Houlden H. Common pathogenic pathways in mpelanoma and Parkinson disease. Neurology,2010,75(11):1653-1655.
[32]Falchi M, Bataille V, Hayward NK, et al. Genome-wide association study identifies variants at 9p21 and 22q13 asso-ciated with development of cutaneous nevi. Nat Genet,2009,41(9):915-919.
[33]Kvaskoff M, Whiteman DC, Zhao ZZ, et al. Polymorphisms in nevus-associated genes MTAP, PLA2G6, and IRF4 and the risk of invasive cutaneous melanoma. Twin Res Hum Genet,2011,14(2):422-432.
[34]Hentze MW, Kuhn LC. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Ndtl Acad Sci U S A,1996,93(9):8175-8182.
[35]Hung HC, Lee EH. MPTP produces differential oxidative stress and antioxidative responses in the nigrostriatal and mesolimbic dopaminergic pathways. Free Radic Biol Med,1998,24(12):76-84.
[36]Ackermann, E. J., E. S. Kempner, and E. A. Dennis. Ca2+-independent cytosolic phospholipase A2 from macrophage-like P388D1 cells. Isolation and characterization. J. Biol. Chem,1994.269(5):9227-9233.
[37]Winstead, M. V., J. Balsinde, and E. A. Dennis. Calciumindependent phospholipase A2:structure and function. Biochim. Biophys. Acta, 2000,1488(12):28-39.
[38]Balsinde J, Balboa MA. Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cells. Cellular Signalling,2005,17(5):1052-1062.
[39]Gregory A, Westaway SK, Holm IE, et al. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology,2008,71(18):1402-1409.
[40]Atsumi G, Tajima M, Hadano A et al. Fas-induced arachidonic acid release is mediated by Ca2+-independent phospholipase A2 but not cytosolic phospholipase A2, which undergoes proteolytic inactivation. J Biol Chem, 1998,273(22):13870-13877.
[41]Balsinde J, Perez R, Balboa MA. Calcium-independent phospholipase A2 and apoptosis. Biochim Biophys Acta,2006,1761(1):1344-1350.
[42]K. Lauber, E. Bohn, S.M. Krober, Y.J. et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell, 2003,113(9)717-730.
[43]Ramanadham S, Hsu FF, Zhang S et al. Apoptosis of insulin-secreting cells induced by endoplasmic reticulum stress is amplified by overexpression of group VIA calcium-independent phospholipase A2 (iPLA2 beta) and suppressed by inhibition of iPLA2 beta. Biochemistry,2004,43(4):918-930.
[44]Peterson B, Knotts T, Cummings BS.Involvement of Ca2+-independent phospholipase A2 isoforms in oxidant-induced neural cell death. Neurotoxicology,2007,28(1):150-160.
[45]Arthur C. R, Morton S. L, Dunham L. D et al. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDMA and no ditterences in heteroplasmic mtDNA mutation abundance. Mol. Neurodegener, 2009,4(1):37-38.
[46]Vilain S, Esposito G, Haddad D. et al. The yeast complex I equivalent NADH dehydrogenase rescues pinkl mutants. PLoS Genet,2012,8:e1002456.
[47]Ottolini D, Cali T, Negro A et al. The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering. Hum Mol Genet,2013,22(11):2152-2168.
[48]Wang M. S, Boddapati S, Emadi S. et al. Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model. BMC Neurosci, 2010,11(1):57-58.
[49]Loeb V, Yakunin E, Saada Aet al. The transgenic overexpression of alpha-synuclein and not its related pathology associates with complex I inhibition. J. Biol. Chem,2010,285(12):7334-7343.
[50]DeMar J. C, Bell J. M. and Rapoport, S. I. Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids. J Biol Chem,2004,91(8):1125-1137.
[51]Williard, D. E., Harmon, S. D., Kaduce, T. L., et al. Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes. J Lipid Res,2001,42(6):1368-1376.
[52]Salem, N., Jr., Litman, B., Kim, H. Y. and Gawrisch, K.Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids,2001,36(12):945-959.
[53]Kim, H. Y.Novel metabolism of docosahexaenoic acid in neural cells. J Biol Chem,2007,282(6):18661-18665.
[54]Schwab, J. M., Chiang, N., Arita, M. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature,2007,447(7):869-874.
[55]Akbar M, Calderon F, Kim HY. Docosahexaenoic acid:a positive modulator of Akt signaling in neuronal survival. Proc Natl Acad Sci U S A, 2005,102(31):10858-10863.
[56]Cole GM, Frautschy SA. Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutr Health, 2006,18(3):249-259.
[57]Verdaguer N, Corbalan-Garcia S, Ochoa WF, et al. Ca2+ bridges the C2 membrane-binding domain of protein kinase Calpha directly to phosphatidylserine. EMBO J,1999,18(22):6329-6338.
[58]Burke RE. Intracellular signalling pathways in dopamine cell death and axonal degeneration. Prog Brain Res,2010,183(4):79-97.
[59]Calandria JM, Bazan NG.Neuroprotectin D1 Modulates the Induction of Pro-Inflammatory Signaling and Promotes Retinal Pigment Epithelial Cell Survival During Oxidative Stress. Adv Exp Med Biol,2010,664(9):663-670.
[60]Zhang C, Bazan NG.Lipid-mediated cell signaling protects against injury and neurodegeneration.J Nutr,2010,140(4):858-863.
[61]Aires V, Hichami A, Filomenko R, et al. Docosahexaenoic acid induces increases in Ca2+ via inositol 1,4,5-triphosphate production and activates protein kinase C gamma and-delta via phosphatidylserine binding site: implication in apoptosis in U937 cells. Mol Pharmacol, 2007,72(7):1545-1556.
[62]Schneider SA, Hardy J, Bhatia KP. Syndromes of neurodegeneration with brain iron accumulation (NBIA):an update on clinical presentations, histological and genetic underpinnings, and treatment considerations. Mov Disord,2012,27(1):42-53.
[63]Schneider SA, Bhatia KP. Syndromes of neurodegeneration with brain iron accumulation. Semin Pediatr Neurol,2012,19(2):57-66.
[64]Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem,2010,345(12):91-104.
[65]Sian-Hulsmann J, Mandel S, Youdim MB, et al. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem,2011,118(6):939-957.
[66]Berg D. In vivo detection of iron and neuromelanin by transcranial sonography--a new approach for early detection of substantia nigra damage. J Neural Transm,2006,113(8),775-780.
[67]Oakley AE, Collingwood JF, Dobson J, et al. Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology, 2007,68(5),1820-1825.
[68]Song N, Jiang H, Wang J, et al. Divalent metal transporter 1 upregulation is involved in the 6-hydroxydopamine induced ferrous iron influx. J Neurosci Res,2007,85(6),3118-3126.
[69]Wang J, Xu H, Jiang H, et al. Neurorescue effect of rosmarinic acid on 6-hydroxydopamine-lesioned nigral dopamine neurons in rat model of Parkinson's disease. J Mol Neurosci,2012,47(1):113-119.
[70]Szyrwiel L, Pap JS, Malinka W, et al. Interactions of anti-Parkinson drug benserazide with Zn(Ⅱ), Cu(Ⅱ), Fe(Ⅱ) ions. J Pharm Biomed Anal,2013, 25(76):36-43.
[71]Wolozin B, Golts N. Iron and Parkinson's disease. Neuroscientist,2002, 8(1):22-32.
[72]Ferrer I, Martinez A, Blanco R et al. Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism:preclinicalParkinson disease. J Neural Transm,2011,118(5):821-839.
[73]Rouault TA, Cooperman S. Brain iron metabolism. Semin Pediatr Neurol, 2006,13(3):142-148.
[74]Sian-Hulsmann J, Mandel S, Youdim MB, et al. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem,2011,118(6):939-957.
[75]Song N, Wang J, Jiang H, Xie J. Ferroportin 1 but not hephaestin contributes to iron accumulation in a cell model of Parkinson's disease. Free Radic Biol Med,2010,48(2):332-341.
[76]Yu X, Du T, Song N, et al. Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson disease. Neurology, 2013,80(5):492-495.
[77]Ward DM, Kaplan J. Ferroportin-mediated iron transport:expression and regulation. Biochim Biophys Acta,2012,1823(9):1426-1433.
[78]Crichton RR, Dexter DT, Ward RJ. Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm,2011,118(3):301-314.
[79]Snyder AM, Connor JR. Iron, the substantia nigra and related neurological disorders. Biochim Biophys Acta,2009,1790(7):606-614.
[80]Ikeda K, Nakamura Y, Kiyozuka T et al. Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson's disease:changes linked to disease progression. Neurodegener Dis,2011,8(4):252-8.
[1]Crichton A. An inquiry into the nature and origin of mental derangement:on attention and its diseases. J Atten Disord,2008,12(3):200-204
[2]Mills E, Dong XP, Wang F, et al. Mechanisms of brain iron transport:insight into neurodegeneration and CNS disorders. Future Med Chem,2010, 2(1):51-64
[3]Levenson CW, Tassabehji NM. Iron and ageing:an introduction to iron regulatory mechanisms. Ageing Res Rev,2004,3(3):251-263.
[4]Crichton RR, Dexter DT, Ward RJ, Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm,2011,118(3):301-314.
[5]Luck AN, Mason AB. Transferrin-mediated cellular iron delivery. Curr Top Membr,2012,69(1):3-35.
[6]Anderson CP, Shen M, Eisenstein RS, et al. Mammalian iron metabolism and its control by iron regulatory proteins. Biochim Biophys Acta,2012,1823(9): 1468-1483.
[7]Leitner DF, Connor JR. Functional roles of transferrin in the brain. Biochim Biophys Acta,2012,1820(3):393-402.
[8]El Hage Chahine JM, Hemadi M, et al. Uptake and release of metal ions by transferrin and interaction with receptor 1. Biochim Biophys Acta, 2012,1820(3):334-347.
[9]Chen J, Enns CA. Hereditary hemochromatosis and transferrin receptor 2. Biochim Biophys Acta,2012,1820(3):256-263.
[10]Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J, 2011,434(3):365-381.
[11]Buu NT, Cellier M, Gros P, et al. Identification of a highly polymorphic length variant in the 3'UTR of NRAMP1. Immunogenetics,1995,42(5):428-429.
[12]Andrews NC. The iron transporter DMT1. Int J Biochem Cell Biol, 1999,31(10):991-994.
[13]H Gunslun, B MacKeuzie, UV Berger, Y, et al.Cloning and characterization of a mammalian proton-coupled metal-ion transporter, Nature,1997,388(11) 482-488.
[14]Zheng W, Monnot AD. Regulation of brain iron and copper homeostasis by brain barrier systems:implication in neurodegenerative diseases. Pharmacol Ther,2012,133(2):177-188.
[15]Gunshin H, Allerson CR, Polycarpou-Schwarz M, et al. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett, 2001,509(2):309-316.
[16]Musallam KM, Cappellini MD, Wood JC, et al. Iron overload in non-transfusion-dependent thalassemia:a clinical perspective. Blood Rev, 2012,26(Suppl 1):S16-19.
[17]Cortese S, Angriman M, Lecendreux M, et al. Iron and attention deficit/hyperactivity disorder:What is the empirical evidence so far? A systematicreview of the literature. Expert Rev Neurother, 2012,12(10):1227-1240.
[18]Abboud S, Haile DJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem,2000,275(26):19906-19912.
[19]Jeong SY, David S. Glycosylphosphatidylinositol-anchored cerulopla-smin is required for iron efflux from cells in the central nervous system. J Biol Chem, 2003,278(29):27144-27148.
[20]Burdo JR, Simpson IA, Menzies S, et al. Regulation of the profile of iron-management proteins in brain microvasculature. J Cereb Blood Flow Metab,2004,24(1):67-74.
[21]Ganz T, Nemeth E. Hepcidin and disorders of iron metabolism. Annu Rev Med, 2011,62(3):347-360.
[22]Frazer DM, Wilkins SJ, Becker EM, et al. A rapid decrease in the expression of DMT1 and Dcytb but not Iregl or hephaestin explains the mucosal block phenomenon of iron absorption. Gut,2003,52(3):340-346.
[23]Ward DM, Kaplan J. Ferroportin-mediated iron transport:expression and regulation. Biochim Biophys Acta,2012,1823(9):1426-1433.
[24]Pantopoulos K, Porwal SK, Tartakoff A, et al. Mechanisms of mammalian iron homeostasis. Biochemistry,2012,51(29):5705-5724.
[25]Graham RM, Chua AC, Herbison CE, et al. Liver iron transport. World J Gastroenterol,2007,13(35):4725-4736.
[26]Lonnerdal B. Calcium and iron absorption--mechanisms and public health relevance. Int J Vitam Nutr Res,2010,80(4-5):293-239.
[27]Anderson CP, Shen M, Eisenstein RS, et al. Mammalian iron metabolism and its control by iron regulatory proteins. Biochim Biophys Acta, 2012,1823(9):1468-1483.
[28]Muckenthaler MU, Galy B, Hentze MW. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr,2008,28(4):197-213.
[29]Tandara L, Salamunic I. Iron metabolism:current facts and future directions. Biochem Med (Zagreb),2012,22(3):311-328.
[30]Rouault TA. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol,2006,2(8):406-414.
[31]Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal,2012,24(5):981-990.
[32]Castellani RJ, Moreira PI, Perry G, et al. The role of iron as a mediator of oxidative stress in Alzheimer disease. Biofactors,2012,38(2):133-138.
[33]Bonda DJ, Lee HG, Blair JA, et al. Role of metal dyshomeostasis in Alzheimer's disease. Metallomics,2011,3(3):267-270.
[34]Huang X, Moir RD, Tanzi RE, et al. Redox-active metals, oxidative stress, and Alzheimer's disease pathology. Ann N Y Acad Sci,2004,1012(10):153-163.
[35]Percy ME, Kruck TP, Pogue Al, et al.Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer's disease. J Inorg Biochem,2011,105(11):1505-1512.
[36]Gille G, Reichmann H. Iron-dependent functions of mitochondria-relation to neurodegeneration. J Neural Transm,2011,118(3):349-359.
[37]Sian-Hulsmann J, Mandel S, Youdim MB, et al. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem,2011,118(6):939-957.
[38]Crichton RR, Dexter DT, Ward RJ. Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm,2011,118(3):301-314.
[39]Quintana C, Gutierrez L. Could a dysfunction of ferritin be a determinant factor in the aetiology of some neurodegenerative diseases? Biochim Biophys Acta,2010,1800(8):770-782
[40]Ozawa T. Neuronal iron accumulation associated with tau deficiency in parkinsonism. Mov Disord,2012,27(7):816.
[41]Parmar A, Khare S, Srivastav V. Pantothenate-kinase associated neurodegeneration. J Assoc Physicians India,2012,60(3):74-76.
[42]Hartig MB, Prokisch H, Meitinger T, et al. Pantothenate kinase-associated neurodegeneration. Curr Drug Targets,2012,13(9):1182-1189.
[43]Singh P, Saggar K, Kaur M, et al. Magnetic resonance imaging in pantothenate kinase-2-associated neurodegeneration. J Pediatr Neurosci,2012,7(1):27-29.
[44]Chang CL, Lin CM. Eye-of-the-Tiger sign is not Pathognomonic of Pantothenate Kinase-Associated Neurodegeneration in Adult Cases. Brain Behav,2011,1(1):55-56.
[45]Szumowski J, Bas E, Gaarder K, et al. Measurement of brain iron distribution in Hallevorden-Spatz syndrome. J Magn Reson Imaging,2010,31(2):482-489.
[46]Brunetti D, Dusi S, Morbin M, et al. Pantothenate kinase-associated neurodegeneration:altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model. Hum Mol Genet, 2012,21(24):5294-5305.
[47]Schulte EC, Claussen MC, Jochim A, et al. Mitochondrial membrane protein associated neurodegenration:A novel variant of neurodegeneration with brain iron accumulation. Mov Disord,2013,28(2):224-227.
[48]Campanella A, Privitera D, Guaraldo M, et al. Skin fibroblasts from pantothenate kinase-associated neurodegeneration patients show altered cellular oxidative status and have defective iron-handling properties. Hum Mol Genet,2012,21(18):4049-4059
[49]Gregory A, Kurian MA, Maher ER, et al. PLA2G6-Associated Neurodegeneration. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA):University of Washington, Seattle; 1993-.2008 Jun 19
[50]Gregory A, Hayflick S. Neurodegeneration with Brain Iron Accumulation Disorders Overview. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA):University of Washington, Seattle; 1993-.2013 Feb 28.
[51]Mader I, Krageloh-Mann I, Seeger U, et al. Proton MR spectroscopy reveals lactate in infantile neuroaxonal dystrophy (INAD). Neuropediatrics, 2001,32(2):97-100.
[52]Nardocci N, Zorzi G, Farina L, et al. Infantile neuroaxonal dystrophy:clinical spectrum and diagnostic criteria. Neurology,1999,52(7):1472-1478.
[53]Tomiyama H, Yoshino H, Ogaki K, et al. PLA2G6 variant in Parkinson's disease. J Hum Genet,2011,56(5):401-403.
[54]Gregory A, Hayflick SJ. Genetics of neurodegeneration with brain iron accumulation. Curr Neurol Neurosci Rep,2011,11(3):254-261.
[55]Kruer MC, Gregory A, Hayflick SJ. Fatty Acid Hydroxylase-Associated Neurodegeneration. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA):University of Washington, Seattle; 1993-2011
[56]Kruer MC, Paudel R, Wagoner W, et al. Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts. Neurosci Lett,2012,523(1):35-38.
[57]Behrens MI, Bruggemann N, Chana P, et al. Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Mov Disord, 2010,25(12):1929-1937.
[58]Usenovic M. Tresse E, Mazzulli JR, et al. Deficiency of ATP 13A2 leads to lysosomal dysfunction,. a-synuclein accumulation, and neurotoxicity. J Neurosci,2012,32(12):4240-4246.
[59]Azuma M, Hirano T, Miyajima H, et al. Regulation of murine IgE production in S JA/9 and nude mice.Potentiation of IgE production by recombinant interleukin 4. J Immunol,1987,139(8):2538-2544.
[60]Kono S. Aceruloplasminemia. Curr Drug Targets,2012,13(9):1190-1199.
[61]Dusek P, Jankovic J, Le W. Iron dysregulation in movement disorders. Neurobiol Dis,2012,46(1):1-18.
[62]White KN, Conesa C, Sanchez L, Amini M, Farnaud S, Lorvoralak C, Evans RW. The transfer of iron between ceruloplasmin and transferrins. Biochim Biophys Acta,2012,1820(3):411-416.
[63]Hineno A, Kaneko K, Yoshida K, et al. Ceruloplasmin protects against rotenone-induced oxidative stress and neurotoxicity. Neurochem Res, 2011,36(11):2127-2135.
[63]Pan VL, Tang HH, Chen Q, et al. Desferrioxamine treatment of aceruloplasminemia:Long-term follow-up. Mov Disord, 2011,26(11):2142-2144.
[65]Curtis AR, Fey C, Morris CM, et al. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet, 2001,28(4):350-354.
[66]Lehn A, Boyle R, Brown H, et al. Neuroferritinopathy. Parkinsonism Relat Disord,2012,18(8):909-915.
[67]McNeill A, Chinnery PF. Neuroferritinopathy:update on clinical features and pathogenesis. Curr Drug Targets,2012,13(9):1200-1203.
[68]Levine SM, Bilgen M, Lynch SG. Iron accumulation in multiple sclerosis:an early pathogenic event. Expert Rev Neurother,2013,13(3):247-250.
[69]Zorzi G, Zibordi F, Chiapparini L, et al. Therapeutic advances in neurodegeneration with brain iron accumulation. Semin Pediatr Neurol, 2012,19(2):82-86.
[70]Hartig MB, Iuso A, Haack T, et al Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet,2011,89(4):543-550.
[71]Goldman JG, Eichenseer SR, Berry-Kravis E, et al. Clinical features of neurodegeneration with brain iron accumulation due to a C19orfl2 gene mutation. Mov Disord,2013 Mar 13.
[72]Banjoko SO, Oseni FA, Togun RA, et al. Iron status in HIV-1 infection: implications in disease pathology. BMC Clin Pathol,2012 Dec 17
[2]Lv Z, Guo J, Sun Q et al. Association between PLA2G6 gene polymorphisms and Parkinson's disease in the Chinese Han population. Parkinsonism Relat Disord,2012,18(5):641-644.
[3]Singleton AB, Farrer M, Johnson J, et al.alpha-Synuclein locus triplication causes Parkinson's disease. Science,2003,302(5646):841
[4]Kitada T, Asakawa S, Hattori N, et al.Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature,1998,392(6676):605-608
[5]Leroy E, Boyer R, Auburger G, et al.The ubiquitin pathway in Parkinson's disease. Nature,1998,395(6701):451-452
[6]Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science,2004,304(5674): 1158-1160
[7]Bonifati V, Rizzu P, van Baren MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science,2003,299(5604):256-259
[8]Zimprich A, Biskup S, Leitner P, et al.Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron,2004, 44(4):601-607
[9]Ramirez A, Heimbach A, Grundemann J, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet,2006,38(10):1184-1191
[10]Lautier C, Goldwurm S, Diirr A, et al. Mutations in the GIGYF2 (TNRC15) gene at the PARK11 locus in familial Parkinson disease.Mutations in the GIGYF2 (TNRC15) gene at the PARK11 locus in familial Parkinson disease. Am J Hum Genet,2008,82(4):822-833
[11]Strauss KM, Martins LM, Plun-Favreau H, et al. Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease. Hum Mol Genet, 2005,14(15):2099-2111
[12]Paisan-Ruiz C, Bhatia KP, Li A, et al.Characterization of PLA2G6 as a Locus for Dystonia-Parkinsonism. Annals of Neurology,2009,65(1):19-23.
[13]Di Fonzo A, Dekker MC, Montagna P, et al. FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology, 2009,72(3):240-245
[14]Hsu LJ, Sagara Y, Arroyo A, et al. alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am J Pathol,2000,157(2):401-410
[15]Volles MJ, Lee SJ, Rochet JC, et al. Vesicle permeabilization by protofibrillar alpha-synuclein:implications for the pathogenesis and treatment of Parkinson's disease. Biochemistry,2001,40(26):7812-7819
[16]Shi CH, Tang BS, Wang L, et al. PLA2G6 gene mutation in autosomal recessive early-onset parkinsonism in a Chinese cohort. Neurology, 2011,77(1):75-81.
[17]Gregory A, Kurian MA, Maher ER, Hogarth P, Hayflick SJ. PLA2G6-Associated Neurodegeneration. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA): University of Washington, Seattle; 1993-.2008 Jun 19 [updated 2012 Apr 19
[18]Gregory A, Westaway SK, Holm IE, et al. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology,2008,71(18):1402-1409.
[19]Lv Z, Jiang H, Xu H et al. Increased iron levels correlate with the selective nigral dopaminergic neuron degeneration in Parkinson's disease. J Neural Transm,2011,118(3):361-369.
[20]Paisan-Ruiz C, Li A, Schneider SA, Holton JL, et al. Widespread Lewy body and tau accumulation in childhood and adult onset dystonia-parkinsonism cases with PLA2G6 mutations. Neurobiol Aging,2012,33(4):814-823.
[21]Kauther KM, Hoft C, Rissling I, et al. The PLA2G6 gene in early-onset Parkinson's disease. Mov Disord,2011,26(3):2415-2417.
[22]Falchi M, Bataille V, Hayward NK et al. Genome-wide association study identifies variants at 9p21 and 22q13 associated with development of cutaneous nevi. Nat Genet,2009,41(8):915 919.
[23]Liu R, Gao X, Lu Y et al. Meta-analysis of the relationship between Parkinson disease and melanoma. Neurology,2011,76(23):2002-2009.
[24]Bertoni JM, Arlette JP, Fernandez HH, et al. North American Parkinson's and Melanoma Survey Investigators. Increased melanoma risk in Parkinson disease: a prospective clinicopathological study. Arch Neurol,2010,67(3):347-352.
[25]Baade PD, Fritschi L, Freedman DM. Mortality due to amyotrophic lateral sclerosis and Parkinson's disease among melanoma patients. Neuroepidemiology,2007,28(3):16-20.
[26]Gao X, Simon KC, Han J, et al. Family history of melanoma and Parkinson disease risk. Neurology,2009,73(1):1286-1291.
[27]Skibba JL, Pinckley J, Gilbert EF, et al. Multiple primary melanoma following administration of levodopa. Arch Pathol,1972,93(3):556-561.
[28]Fiala KH, Whetteckey J, Manyam BV. Malignant melanoma and levodopa in Parkinson's disease:causality or coincidence? Parkinsonism Relat Disord, 2003,9(1):321-327.
[29]Millikin D, Meese E, Vogelstein B, et al. Loss of heterozygosity for loci on the long arm of chromosome 6 in human malignant melanoma. Cancer Res, 1991,51(6):5449-5453.
[30]Fasano M, Giraudo S, Coha S, et al. Residual substantia nigra neuromelanin in Parkinson's disease is cross-linked to alpha-synuclein. Neurochem Int, 2003,42(3):603-606.
[31]Paisn-Ruiz C, Houlden H. Common pathogenic pathways in mpelanoma and Parkinson disease. Neurology,2010,75(11):1653-1655.
[32]Falchi M, Bataille V, Hayward NK, et al. Genome-wide association study identifies variants at 9p21 and 22q13 asso-ciated with development of cutaneous nevi. Nat Genet,2009,41(9):915-919.
[33]Kvaskoff M, Whiteman DC, Zhao ZZ, et al. Polymorphisms in nevus-associated genes MTAP, PLA2G6, and IRF4 and the risk of invasive cutaneous melanoma. Twin Res Hum Genet,2011,14(2):422-432.
[34]Hentze MW, Kuhn LC. Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. Proc Ndtl Acad Sci U S A,1996,93(9):8175-8182.
[35]Hung HC, Lee EH. MPTP produces differential oxidative stress and antioxidative responses in the nigrostriatal and mesolimbic dopaminergic pathways. Free Radic Biol Med,1998,24(12):76-84.
[36]Ackermann, E. J., E. S. Kempner, and E. A. Dennis. Ca2+-independent cytosolic phospholipase A2 from macrophage-like P388D1 cells. Isolation and characterization. J. Biol. Chem,1994.269(5):9227-9233.
[37]Winstead, M. V., J. Balsinde, and E. A. Dennis. Calciumindependent phospholipase A2:structure and function. Biochim. Biophys. Acta, 2000,1488(12):28-39.
[38]Balsinde J, Balboa MA. Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cells. Cellular Signalling,2005,17(5):1052-1062.
[39]Gregory A, Westaway SK, Holm IE, et al. Neurodegeneration associated with genetic defects in phospholipase A2. Neurology,2008,71(18):1402-1409.
[40]Atsumi G, Tajima M, Hadano A et al. Fas-induced arachidonic acid release is mediated by Ca2+-independent phospholipase A2 but not cytosolic phospholipase A2, which undergoes proteolytic inactivation. J Biol Chem, 1998,273(22):13870-13877.
[41]Balsinde J, Perez R, Balboa MA. Calcium-independent phospholipase A2 and apoptosis. Biochim Biophys Acta,2006,1761(1):1344-1350.
[42]K. Lauber, E. Bohn, S.M. Krober, Y.J. et al. Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell, 2003,113(9)717-730.
[43]Ramanadham S, Hsu FF, Zhang S et al. Apoptosis of insulin-secreting cells induced by endoplasmic reticulum stress is amplified by overexpression of group VIA calcium-independent phospholipase A2 (iPLA2 beta) and suppressed by inhibition of iPLA2 beta. Biochemistry,2004,43(4):918-930.
[44]Peterson B, Knotts T, Cummings BS.Involvement of Ca2+-independent phospholipase A2 isoforms in oxidant-induced neural cell death. Neurotoxicology,2007,28(1):150-160.
[45]Arthur C. R, Morton S. L, Dunham L. D et al. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDMA and no ditterences in heteroplasmic mtDNA mutation abundance. Mol. Neurodegener, 2009,4(1):37-38.
[46]Vilain S, Esposito G, Haddad D. et al. The yeast complex I equivalent NADH dehydrogenase rescues pinkl mutants. PLoS Genet,2012,8:e1002456.
[47]Ottolini D, Cali T, Negro A et al. The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering. Hum Mol Genet,2013,22(11):2152-2168.
[48]Wang M. S, Boddapati S, Emadi S. et al. Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model. BMC Neurosci, 2010,11(1):57-58.
[49]Loeb V, Yakunin E, Saada Aet al. The transgenic overexpression of alpha-synuclein and not its related pathology associates with complex I inhibition. J. Biol. Chem,2010,285(12):7334-7343.
[50]DeMar J. C, Bell J. M. and Rapoport, S. I. Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids. J Biol Chem,2004,91(8):1125-1137.
[51]Williard, D. E., Harmon, S. D., Kaduce, T. L., et al. Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes. J Lipid Res,2001,42(6):1368-1376.
[52]Salem, N., Jr., Litman, B., Kim, H. Y. and Gawrisch, K.Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids,2001,36(12):945-959.
[53]Kim, H. Y.Novel metabolism of docosahexaenoic acid in neural cells. J Biol Chem,2007,282(6):18661-18665.
[54]Schwab, J. M., Chiang, N., Arita, M. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature,2007,447(7):869-874.
[55]Akbar M, Calderon F, Kim HY. Docosahexaenoic acid:a positive modulator of Akt signaling in neuronal survival. Proc Natl Acad Sci U S A, 2005,102(31):10858-10863.
[56]Cole GM, Frautschy SA. Docosahexaenoic acid protects from amyloid and dendritic pathology in an Alzheimer's disease mouse model. Nutr Health, 2006,18(3):249-259.
[57]Verdaguer N, Corbalan-Garcia S, Ochoa WF, et al. Ca2+ bridges the C2 membrane-binding domain of protein kinase Calpha directly to phosphatidylserine. EMBO J,1999,18(22):6329-6338.
[58]Burke RE. Intracellular signalling pathways in dopamine cell death and axonal degeneration. Prog Brain Res,2010,183(4):79-97.
[59]Calandria JM, Bazan NG.Neuroprotectin D1 Modulates the Induction of Pro-Inflammatory Signaling and Promotes Retinal Pigment Epithelial Cell Survival During Oxidative Stress. Adv Exp Med Biol,2010,664(9):663-670.
[60]Zhang C, Bazan NG.Lipid-mediated cell signaling protects against injury and neurodegeneration.J Nutr,2010,140(4):858-863.
[61]Aires V, Hichami A, Filomenko R, et al. Docosahexaenoic acid induces increases in Ca2+ via inositol 1,4,5-triphosphate production and activates protein kinase C gamma and-delta via phosphatidylserine binding site: implication in apoptosis in U937 cells. Mol Pharmacol, 2007,72(7):1545-1556.
[62]Schneider SA, Hardy J, Bhatia KP. Syndromes of neurodegeneration with brain iron accumulation (NBIA):an update on clinical presentations, histological and genetic underpinnings, and treatment considerations. Mov Disord,2012,27(1):42-53.
[63]Schneider SA, Bhatia KP. Syndromes of neurodegeneration with brain iron accumulation. Semin Pediatr Neurol,2012,19(2):57-66.
[64]Jomova K, Vondrakova D, Lawson M, Valko M. Metals, oxidative stress and neurodegenerative disorders. Mol Cell Biochem,2010,345(12):91-104.
[65]Sian-Hulsmann J, Mandel S, Youdim MB, et al. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem,2011,118(6):939-957.
[66]Berg D. In vivo detection of iron and neuromelanin by transcranial sonography--a new approach for early detection of substantia nigra damage. J Neural Transm,2006,113(8),775-780.
[67]Oakley AE, Collingwood JF, Dobson J, et al. Individual dopaminergic neurons show raised iron levels in Parkinson disease. Neurology, 2007,68(5),1820-1825.
[68]Song N, Jiang H, Wang J, et al. Divalent metal transporter 1 upregulation is involved in the 6-hydroxydopamine induced ferrous iron influx. J Neurosci Res,2007,85(6),3118-3126.
[69]Wang J, Xu H, Jiang H, et al. Neurorescue effect of rosmarinic acid on 6-hydroxydopamine-lesioned nigral dopamine neurons in rat model of Parkinson's disease. J Mol Neurosci,2012,47(1):113-119.
[70]Szyrwiel L, Pap JS, Malinka W, et al. Interactions of anti-Parkinson drug benserazide with Zn(Ⅱ), Cu(Ⅱ), Fe(Ⅱ) ions. J Pharm Biomed Anal,2013, 25(76):36-43.
[71]Wolozin B, Golts N. Iron and Parkinson's disease. Neuroscientist,2002, 8(1):22-32.
[72]Ferrer I, Martinez A, Blanco R et al. Neuropathology of sporadic Parkinson disease before the appearance of parkinsonism:preclinicalParkinson disease. J Neural Transm,2011,118(5):821-839.
[73]Rouault TA, Cooperman S. Brain iron metabolism. Semin Pediatr Neurol, 2006,13(3):142-148.
[74]Sian-Hulsmann J, Mandel S, Youdim MB, et al. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem,2011,118(6):939-957.
[75]Song N, Wang J, Jiang H, Xie J. Ferroportin 1 but not hephaestin contributes to iron accumulation in a cell model of Parkinson's disease. Free Radic Biol Med,2010,48(2):332-341.
[76]Yu X, Du T, Song N, et al. Decreased iron levels in the temporal cortex in postmortem human brains with Parkinson disease. Neurology, 2013,80(5):492-495.
[77]Ward DM, Kaplan J. Ferroportin-mediated iron transport:expression and regulation. Biochim Biophys Acta,2012,1823(9):1426-1433.
[78]Crichton RR, Dexter DT, Ward RJ. Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm,2011,118(3):301-314.
[79]Snyder AM, Connor JR. Iron, the substantia nigra and related neurological disorders. Biochim Biophys Acta,2009,1790(7):606-614.
[80]Ikeda K, Nakamura Y, Kiyozuka T et al. Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson's disease:changes linked to disease progression. Neurodegener Dis,2011,8(4):252-8.
[1]Crichton A. An inquiry into the nature and origin of mental derangement:on attention and its diseases. J Atten Disord,2008,12(3):200-204
[2]Mills E, Dong XP, Wang F, et al. Mechanisms of brain iron transport:insight into neurodegeneration and CNS disorders. Future Med Chem,2010, 2(1):51-64
[3]Levenson CW, Tassabehji NM. Iron and ageing:an introduction to iron regulatory mechanisms. Ageing Res Rev,2004,3(3):251-263.
[4]Crichton RR, Dexter DT, Ward RJ, Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm,2011,118(3):301-314.
[5]Luck AN, Mason AB. Transferrin-mediated cellular iron delivery. Curr Top Membr,2012,69(1):3-35.
[6]Anderson CP, Shen M, Eisenstein RS, et al. Mammalian iron metabolism and its control by iron regulatory proteins. Biochim Biophys Acta,2012,1823(9): 1468-1483.
[7]Leitner DF, Connor JR. Functional roles of transferrin in the brain. Biochim Biophys Acta,2012,1820(3):393-402.
[8]El Hage Chahine JM, Hemadi M, et al. Uptake and release of metal ions by transferrin and interaction with receptor 1. Biochim Biophys Acta, 2012,1820(3):334-347.
[9]Chen J, Enns CA. Hereditary hemochromatosis and transferrin receptor 2. Biochim Biophys Acta,2012,1820(3):256-263.
[10]Wang J, Pantopoulos K. Regulation of cellular iron metabolism. Biochem J, 2011,434(3):365-381.
[11]Buu NT, Cellier M, Gros P, et al. Identification of a highly polymorphic length variant in the 3'UTR of NRAMP1. Immunogenetics,1995,42(5):428-429.
[12]Andrews NC. The iron transporter DMT1. Int J Biochem Cell Biol, 1999,31(10):991-994.
[13]H Gunslun, B MacKeuzie, UV Berger, Y, et al.Cloning and characterization of a mammalian proton-coupled metal-ion transporter, Nature,1997,388(11) 482-488.
[14]Zheng W, Monnot AD. Regulation of brain iron and copper homeostasis by brain barrier systems:implication in neurodegenerative diseases. Pharmacol Ther,2012,133(2):177-188.
[15]Gunshin H, Allerson CR, Polycarpou-Schwarz M, et al. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett, 2001,509(2):309-316.
[16]Musallam KM, Cappellini MD, Wood JC, et al. Iron overload in non-transfusion-dependent thalassemia:a clinical perspective. Blood Rev, 2012,26(Suppl 1):S16-19.
[17]Cortese S, Angriman M, Lecendreux M, et al. Iron and attention deficit/hyperactivity disorder:What is the empirical evidence so far? A systematicreview of the literature. Expert Rev Neurother, 2012,12(10):1227-1240.
[18]Abboud S, Haile DJ. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem,2000,275(26):19906-19912.
[19]Jeong SY, David S. Glycosylphosphatidylinositol-anchored cerulopla-smin is required for iron efflux from cells in the central nervous system. J Biol Chem, 2003,278(29):27144-27148.
[20]Burdo JR, Simpson IA, Menzies S, et al. Regulation of the profile of iron-management proteins in brain microvasculature. J Cereb Blood Flow Metab,2004,24(1):67-74.
[21]Ganz T, Nemeth E. Hepcidin and disorders of iron metabolism. Annu Rev Med, 2011,62(3):347-360.
[22]Frazer DM, Wilkins SJ, Becker EM, et al. A rapid decrease in the expression of DMT1 and Dcytb but not Iregl or hephaestin explains the mucosal block phenomenon of iron absorption. Gut,2003,52(3):340-346.
[23]Ward DM, Kaplan J. Ferroportin-mediated iron transport:expression and regulation. Biochim Biophys Acta,2012,1823(9):1426-1433.
[24]Pantopoulos K, Porwal SK, Tartakoff A, et al. Mechanisms of mammalian iron homeostasis. Biochemistry,2012,51(29):5705-5724.
[25]Graham RM, Chua AC, Herbison CE, et al. Liver iron transport. World J Gastroenterol,2007,13(35):4725-4736.
[26]Lonnerdal B. Calcium and iron absorption--mechanisms and public health relevance. Int J Vitam Nutr Res,2010,80(4-5):293-239.
[27]Anderson CP, Shen M, Eisenstein RS, et al. Mammalian iron metabolism and its control by iron regulatory proteins. Biochim Biophys Acta, 2012,1823(9):1468-1483.
[28]Muckenthaler MU, Galy B, Hentze MW. Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr,2008,28(4):197-213.
[29]Tandara L, Salamunic I. Iron metabolism:current facts and future directions. Biochem Med (Zagreb),2012,22(3):311-328.
[30]Rouault TA. The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol,2006,2(8):406-414.
[31]Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal,2012,24(5):981-990.
[32]Castellani RJ, Moreira PI, Perry G, et al. The role of iron as a mediator of oxidative stress in Alzheimer disease. Biofactors,2012,38(2):133-138.
[33]Bonda DJ, Lee HG, Blair JA, et al. Role of metal dyshomeostasis in Alzheimer's disease. Metallomics,2011,3(3):267-270.
[34]Huang X, Moir RD, Tanzi RE, et al. Redox-active metals, oxidative stress, and Alzheimer's disease pathology. Ann N Y Acad Sci,2004,1012(10):153-163.
[35]Percy ME, Kruck TP, Pogue Al, et al.Towards the prevention of potential aluminum toxic effects and an effective treatment for Alzheimer's disease. J Inorg Biochem,2011,105(11):1505-1512.
[36]Gille G, Reichmann H. Iron-dependent functions of mitochondria-relation to neurodegeneration. J Neural Transm,2011,118(3):349-359.
[37]Sian-Hulsmann J, Mandel S, Youdim MB, et al. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem,2011,118(6):939-957.
[38]Crichton RR, Dexter DT, Ward RJ. Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm,2011,118(3):301-314.
[39]Quintana C, Gutierrez L. Could a dysfunction of ferritin be a determinant factor in the aetiology of some neurodegenerative diseases? Biochim Biophys Acta,2010,1800(8):770-782
[40]Ozawa T. Neuronal iron accumulation associated with tau deficiency in parkinsonism. Mov Disord,2012,27(7):816.
[41]Parmar A, Khare S, Srivastav V. Pantothenate-kinase associated neurodegeneration. J Assoc Physicians India,2012,60(3):74-76.
[42]Hartig MB, Prokisch H, Meitinger T, et al. Pantothenate kinase-associated neurodegeneration. Curr Drug Targets,2012,13(9):1182-1189.
[43]Singh P, Saggar K, Kaur M, et al. Magnetic resonance imaging in pantothenate kinase-2-associated neurodegeneration. J Pediatr Neurosci,2012,7(1):27-29.
[44]Chang CL, Lin CM. Eye-of-the-Tiger sign is not Pathognomonic of Pantothenate Kinase-Associated Neurodegeneration in Adult Cases. Brain Behav,2011,1(1):55-56.
[45]Szumowski J, Bas E, Gaarder K, et al. Measurement of brain iron distribution in Hallevorden-Spatz syndrome. J Magn Reson Imaging,2010,31(2):482-489.
[46]Brunetti D, Dusi S, Morbin M, et al. Pantothenate kinase-associated neurodegeneration:altered mitochondria membrane potential and defective respiration in Pank2 knock-out mouse model. Hum Mol Genet, 2012,21(24):5294-5305.
[47]Schulte EC, Claussen MC, Jochim A, et al. Mitochondrial membrane protein associated neurodegenration:A novel variant of neurodegeneration with brain iron accumulation. Mov Disord,2013,28(2):224-227.
[48]Campanella A, Privitera D, Guaraldo M, et al. Skin fibroblasts from pantothenate kinase-associated neurodegeneration patients show altered cellular oxidative status and have defective iron-handling properties. Hum Mol Genet,2012,21(18):4049-4059
[49]Gregory A, Kurian MA, Maher ER, et al. PLA2G6-Associated Neurodegeneration. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA):University of Washington, Seattle; 1993-.2008 Jun 19
[50]Gregory A, Hayflick S. Neurodegeneration with Brain Iron Accumulation Disorders Overview. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA):University of Washington, Seattle; 1993-.2013 Feb 28.
[51]Mader I, Krageloh-Mann I, Seeger U, et al. Proton MR spectroscopy reveals lactate in infantile neuroaxonal dystrophy (INAD). Neuropediatrics, 2001,32(2):97-100.
[52]Nardocci N, Zorzi G, Farina L, et al. Infantile neuroaxonal dystrophy:clinical spectrum and diagnostic criteria. Neurology,1999,52(7):1472-1478.
[53]Tomiyama H, Yoshino H, Ogaki K, et al. PLA2G6 variant in Parkinson's disease. J Hum Genet,2011,56(5):401-403.
[54]Gregory A, Hayflick SJ. Genetics of neurodegeneration with brain iron accumulation. Curr Neurol Neurosci Rep,2011,11(3):254-261.
[55]Kruer MC, Gregory A, Hayflick SJ. Fatty Acid Hydroxylase-Associated Neurodegeneration. In:Pagon RA, Bird TD, Dolan CR, Stephens K, Adam MP, editors. GeneReviewsTM [Internet]. Seattle (WA):University of Washington, Seattle; 1993-2011
[56]Kruer MC, Paudel R, Wagoner W, et al. Analysis of ATP13A2 in large neurodegeneration with brain iron accumulation (NBIA) and dystonia-parkinsonism cohorts. Neurosci Lett,2012,523(1):35-38.
[57]Behrens MI, Bruggemann N, Chana P, et al. Clinical spectrum of Kufor-Rakeb syndrome in the Chilean kindred with ATP13A2 mutations. Mov Disord, 2010,25(12):1929-1937.
[58]Usenovic M. Tresse E, Mazzulli JR, et al. Deficiency of ATP 13A2 leads to lysosomal dysfunction,. a-synuclein accumulation, and neurotoxicity. J Neurosci,2012,32(12):4240-4246.
[59]Azuma M, Hirano T, Miyajima H, et al. Regulation of murine IgE production in S JA/9 and nude mice.Potentiation of IgE production by recombinant interleukin 4. J Immunol,1987,139(8):2538-2544.
[60]Kono S. Aceruloplasminemia. Curr Drug Targets,2012,13(9):1190-1199.
[61]Dusek P, Jankovic J, Le W. Iron dysregulation in movement disorders. Neurobiol Dis,2012,46(1):1-18.
[62]White KN, Conesa C, Sanchez L, Amini M, Farnaud S, Lorvoralak C, Evans RW. The transfer of iron between ceruloplasmin and transferrins. Biochim Biophys Acta,2012,1820(3):411-416.
[63]Hineno A, Kaneko K, Yoshida K, et al. Ceruloplasmin protects against rotenone-induced oxidative stress and neurotoxicity. Neurochem Res, 2011,36(11):2127-2135.
[63]Pan VL, Tang HH, Chen Q, et al. Desferrioxamine treatment of aceruloplasminemia:Long-term follow-up. Mov Disord, 2011,26(11):2142-2144.
[65]Curtis AR, Fey C, Morris CM, et al. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet, 2001,28(4):350-354.
[66]Lehn A, Boyle R, Brown H, et al. Neuroferritinopathy. Parkinsonism Relat Disord,2012,18(8):909-915.
[67]McNeill A, Chinnery PF. Neuroferritinopathy:update on clinical features and pathogenesis. Curr Drug Targets,2012,13(9):1200-1203.
[68]Levine SM, Bilgen M, Lynch SG. Iron accumulation in multiple sclerosis:an early pathogenic event. Expert Rev Neurother,2013,13(3):247-250.
[69]Zorzi G, Zibordi F, Chiapparini L, et al. Therapeutic advances in neurodegeneration with brain iron accumulation. Semin Pediatr Neurol, 2012,19(2):82-86.
[70]Hartig MB, Iuso A, Haack T, et al Absence of an orphan mitochondrial protein, c19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. Am J Hum Genet,2011,89(4):543-550.
[71]Goldman JG, Eichenseer SR, Berry-Kravis E, et al. Clinical features of neurodegeneration with brain iron accumulation due to a C19orfl2 gene mutation. Mov Disord,2013 Mar 13.
[72]Banjoko SO, Oseni FA, Togun RA, et al. Iron status in HIV-1 infection: implications in disease pathology. BMC Clin Pathol,2012 Dec 17