过氧化物酶体增殖物激活受体在视神经保护中的作用
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摘要
视神经具有损伤后不可修复再生的特殊性。在视神经相关疾病中,视网膜神经节细胞坏死、凋亡、轴突丢失,继而导致不可逆性的视觉损伤。过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptors,PPARs)经相应配体激活后,对外周器官及中枢神经系统急慢性损伤具有潜在的神经保护作用。视神经属间脑白质在外周的延伸,其病理生理过程与中枢神经系统具有相似之处,从而使PPARs在视神经保护中的作用成为眼科领域关注的热点。文章就PPARs在眼科领域对视神经损伤的保护作用及其可能机制的研究进展进行综述。
Neuronal death is thought to be irreversible. In optic nerve-related diseases, the death and axonal loss of retinal ganglion cells could lead to irreversible visual impairment. A large number of studies support the hypothesis that the peroxisome proliferator-activated receptors(PPARs), once activated by particular ligands, could have a potential neuroprotective effect on the peripheral organs and the central nervous system suffering from acute or chronic injury. Optic nerve belongs to the extension of white matter in the central nervous system and shares similar pathophysiological processes with the central nervous system, which makes PPARs a hot spot in the field of optic nerve protection. This paper reviewed the effect of PPARs in optic nerve protection and its possible mechanism.
Neuronal death is thought to be irreversible. In optic nerve-related diseases, the death and axonal loss of retinal ganglion cells could lead to irreversible visual impairment. A large number of studies support the hypothesis that the peroxisome proliferator-activated receptors(PPARs), once activated by particular ligands, could have a potential neuroprotective effect on the peripheral organs and the central nervous system suffering from acute or chronic injury. Optic nerve belongs to the extension of white matter in the central nervous system and shares similar pathophysiological processes with the central nervous system, which makes PPARs a hot spot in the field of optic nerve protection. This paper reviewed the effect of PPARs in optic nerve protection and its possible mechanism.
引文
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[29]Jung TW,Lee JY,Shim WS,et al.Rosiglitazone protects human neuroblastoma SH-SY5Y cells against MPP+induced cytotoxicity via inhibition of mitochondrial dysfunction and ROS production[J].J Neurol Sci,2007,253(1-2):53.
[30]Song W,Song Y,Kincaid B,et al.Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons:neuroprotection by SIRT3 and PGC-1α[J].Neurobiol Dis,2013,51:72.
[31]Noh YH,Kim KY,Shim MS,et al.Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes[J].Cell Death Dis,2013,4(10):e820.
[32]Doonan F,Wallace DC,Cotter T.Rosiglitazone acts as a neuroprotectant in retinal cells via up-regulation of sestrin-1 and SOD-2[J].J Neurochem,2009,109(2):631-643.
[33]Aoun P,Simpkins JW,Agarwal N.Role of PPAR-γligands in neuroprotection against glutamate-induced cytotoxicity in retinal ganglion cells[J].Invest Ophthalmol Vis Sci,2003,44(7):2999-3004.
[34]Lefebvre P,Chinetti G,Fruchart J C,et al.Sorting out the roles of PPARαin energy metabolism and vascular homeostasis[J].J Clin Invest,2006,116(3):571-580.
[35]Chaturvedi RK,Beal MF.Mitochondrial diseases of the brain[J].Free Rad Biol Med,2013,63(10):1.
[36]Ershov AV,Bazan NG.Photoreceptor phagocytosis selectively activates PPARγexpression in retinal pigment epithelial cells[J].J Neurosci Res,2000,60(3):328-337.
[2]Tan CK,Yan Z,Wahli W.Synthetic and natural peroxisome proliferatoractivated receptor(PPAR)agonists as candidates for the therapy of the metabolic syndrome[J].Exp Opin Therap Targ,2017,21(3):333-348.
[3]Aleshin S,Strokin M,Sergeeva M,et al.Peroxisome proliferator-activated receptor(PPAR)β/δ,a possible nexus of PPARα-and PPARγ-dependent molecular pathways in neurodegenerative diseases:review and novel hypotheses[J].Neurochem Int,2013,63(4):322-330.
[4]Derosa G,Sahebkar A,Maffioli P.The role of various peroxisome proliferatoractivated receptors and their ligands in clinical practice[J].J Cell Physiol,2018,233(1):153-161.
[5]Braissant O,Foufelle F,Scotto C,et al.Differential expression of peroxisome proliferator-activated receptors(PPARs):tissue distribution of PPAR-α,-β,and-γin the adult rat[J].Endocrinology,1996,137(1):354-366.
[6]Michalik L,Auwerx J,Berger JP,et al.International union of pharmacology.LXI.Peroxisome proliferator-activated receptors[J].Pharmacol Rev,2006,58:726-741.
[7]Carta AR,Simuni T.Thiazolidinediones under preclinical and early clinical development for the treatment of Parkinson's disease[J].Expert Opin Investig Drugs,2015,24(2):219-227.
[8]Bernardo A,Levi G,Minghetti L.Role of the peroxisome proliferatoractivated receptor-gamma(PPAR-γ)and its natural ligand 15-deoxy-Delta12,14-prostaglandin J2 in the regulation of microglial functions[J].Eur J Neurosci,2000,12(7):2215.
[9]Owen GI,Zelent A.Origin and evolutionary diversification of the nuclear receptor superfamily[J].Cell Mol Life Sci,2000,57(5):809-827.
[10]任润健,赵虎,毕波.过氧化物酶体增殖物激活受体γ在炎症相关疾病中作用的研究进展[J].检验医学,2017,32(2):153-157.
[11]Georgiadis I,Karatzas T,Korou LM,et al.Beneficial health effects of Chios Gum Mastic and peroxisome proliferator-activated receptors:indications of common mechanisms[J].J Med Food,2015,18(1):1.
[12]Neels JG,Grimaldi PA.Physiological functions of peroxisome proliferatoractivated receptorβ[J].Physiol Rev,2014,94(3):795-858.
[13]Zhang J,Liu X,Xie X,et al.Multitargeted bioactive ligands for PPARs discovered in the last decade[J].Chem Biol Drug Design,2016,88(5):635-663.
[14]Moreno S,Farioli-Vecchioli S,CerùMP.Immunolocalization of peroxisome proliferator-activated receptors and retinoid X receptors in the adult rat CNS[J].Neuroscience,2004,123(1):131-145.
[15]Ramanan S,Kooshki M,Zhao W,et al.PPARαligands inhibit radiationinduced microglial inflammatory responses by negatively regulating NF-κBand AP-1 pathways[J].Free Rad Biol Med,2008,45(12):1695-1704.
[16]Mckenna NJ,O'Malley BW.Combinatorial control of gene expression by nuclear receptors and coregulators[J].Cell,2002,108(4):465.
[17]Qin ZH,Tao LY,Chen X.Dual roles of NF-κB in cell survival and implications of NF-κB inhibitors in neuroprotective therapy[J].Acta Pharmacol Sin,2007,28(12):1859-1872.
[18]Carta AR,Frau L,Pisanu A,et al.Rosiglitazone decreases peroxisome proliferator receptor-γlevels in microglia and inhibits TNF-αproduction:new evidences on neuroprotection in a progressive Parkinson's disease model[J].Neuroscience,2011,194:250.
[19]Sadeghian M,Marinova-Mutafchieva L,Broom L,et al.Full and partial peroxisome proliferation-activated receptor-γagonists,but notδagonist,rescue of dopaminergic neurons in the 6-OHDA parkinsonian model is associated with inhibition of microglial activation and MMP expression[J].J Neuroimmunol,2012,246(1-2):69.
[20]Baregamian N,Mourot JM,Ballard AR,et al.PPAR-γagonist protects against intestinal injury during necrotizing enterocolitis[J].Biochem Biophys Res Commun,2009,379(2):423-427.
[21]Abraki SB,Khalaj L,Shaerzadeh F,et al.Simultaneous inhibition of COX-2 and activation of PPAR-γresulted in the same level and pattern of neuroprotection as they were targeted separately[J].J Mol Neurosci,2013,49(1):116-129.
[22]Freitag CM,Miller RJ.Peroxisome proliferator-activated receptor agonists modulate neuropathic pain:a link to chemokines?[J].Front Cell Neurosci,2014,8:238.
[23]Enayatfard L,Rostami F,Nasoohi S,et al.Dual role of PPAR-γin induction and expression of behavioral sensitization to cannabinoid receptor agonist WIN55,212-2[J].Neuromol Med,2013,15(3):523-535.
[24]Jiang Q,Heneka M,Landreth DGE.The role of peroxisome proliferatoractivated receptor-γ(PPARγ)in Alzheimer's disease[J].Cns Drugs,2008,22(1):1-14.
[25]Schnegg CI,Kooshki M,Hsu FC,et al.PPARδprevents radiation-induced proinflammatory responses in microglia via transrepression of NF-κB and inhibition of the PKCα/MEK1/2/ERK1/2/AP-1 pathway[J].Free Rad Biol Med,2012,52(9):1734-1743.
[26]Zhang XY,Xiao YQ,Zhang Y,et al.Protective effect of pioglitazone on retinal ischemia/reperfusion injury in rats[J].Invest Ophthalmol Vis Sci,2013,54(6):3912-3921.
[27]Zhu J,Zhang J,Ji M,et al.The role of peroxisome proliferator-activated receptor and effects of its agonist,pioglitazone,on a rat model of optic nerve crush:PPARγin retinal neuroprotection[J].PLo S One,2013,8(7):e68935.
[28]Dentesano G,Serratosa J,Tusell JM,et al.CD200R1 and CD200 expression are regulated by PPAR-γin activated glial cells[J].Glia,2014,62(6):982.
[29]Jung TW,Lee JY,Shim WS,et al.Rosiglitazone protects human neuroblastoma SH-SY5Y cells against MPP+induced cytotoxicity via inhibition of mitochondrial dysfunction and ROS production[J].J Neurol Sci,2007,253(1-2):53.
[30]Song W,Song Y,Kincaid B,et al.Mutant SOD1G93A triggers mitochondrial fragmentation in spinal cord motor neurons:neuroprotection by SIRT3 and PGC-1α[J].Neurobiol Dis,2013,51:72.
[31]Noh YH,Kim KY,Shim MS,et al.Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes[J].Cell Death Dis,2013,4(10):e820.
[32]Doonan F,Wallace DC,Cotter T.Rosiglitazone acts as a neuroprotectant in retinal cells via up-regulation of sestrin-1 and SOD-2[J].J Neurochem,2009,109(2):631-643.
[33]Aoun P,Simpkins JW,Agarwal N.Role of PPAR-γligands in neuroprotection against glutamate-induced cytotoxicity in retinal ganglion cells[J].Invest Ophthalmol Vis Sci,2003,44(7):2999-3004.
[34]Lefebvre P,Chinetti G,Fruchart J C,et al.Sorting out the roles of PPARαin energy metabolism and vascular homeostasis[J].J Clin Invest,2006,116(3):571-580.
[35]Chaturvedi RK,Beal MF.Mitochondrial diseases of the brain[J].Free Rad Biol Med,2013,63(10):1.
[36]Ershov AV,Bazan NG.Photoreceptor phagocytosis selectively activates PPARγexpression in retinal pigment epithelial cells[J].J Neurosci Res,2000,60(3):328-337.