Differences between normal and alpha-synuclein overexpressing SH-SY5Y neuroblastoma cells after Aβ(1-42) and NAC treatment
- 作者：Á ; kos Hunya ; Istvá ; n Fö ; ldi ; Viktor Szegedi ; Katalin Soó ; s ; Má ; rta Zará ; ndi ; Antal Szabó ; Dé ; nes Zá ; dori ; Botond Penke ; Zsolt L. Datki
- 关键词：Alpha-synuclein ; Beta-amyloid ; NAC ; SH-SY5Y ; Alzheimer's disease ; Parkinson's disease
- 刊名：Brain Research Bulletin
- 出版年：2008
- 期刊代码：9_03619230
- 类别：neu
- 出版时间：28 March 2008
- 卷：75
- 期：5
- 页码：648-654
- 文件大小：638 K
摘要
Alpha-synuclein (
SN) plays a major role in numerous neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Intracellular inclusions containing aggregated SN have been reported in Alzheimer's and Parkinson's affected brains. Moreover, a proteolytic fragment of SN, the so-called non-amyloid component of Alzheimer's disease amyloid (NAC) was found to be an integral part of Alzheimer's dementia related plaques. Despite the extensive research on this topic, the exact toxic mechanism of SN remains elusive. We have taken the advantage of an SN overexpressing SH-SY5Y cell line and investigated the effects of classical apoptotic factors (e.g. H2O2, amphotericin B and ruthenium red) and aggregated disease-related peptides on cell viability compared to wild type neuroblastoma cells. It was found that SN overexpressing cells are more sensitive to aggregated peptides treatment than normal expressing counterparts. In contrast, cells containing elevated amount of SN were less vulnerable to classical apoptotic stressors than wild type cells. In addition, SN overexpression is accompanied by altered phenotype, attenuated proliferation kinetics, increased neurite arborisation and decreased cell motility. Based on these results, the SN overexpressing cell lines may represent a good and effective in vitro model for Alzheimer's and Parkinson's disease.
SN) plays a major role in numerous neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. Intracellular inclusions containing aggregated SN have been reported in Alzheimer's and Parkinson's affected brains. Moreover, a proteolytic fragment of SN, the so-called non-amyloid component of Alzheimer's disease amyloid (NAC) was found to be an integral part of Alzheimer's dementia related plaques. Despite the extensive research on this topic, the exact toxic mechanism of SN remains elusive. We have taken the advantage of an SN overexpressing SH-SY5Y cell line and investigated the effects of classical apoptotic factors (e.g. H2O2, amphotericin B and ruthenium red) and aggregated disease-related peptides on cell viability compared to wild type neuroblastoma cells. It was found that SN overexpressing cells are more sensitive to aggregated peptides treatment than normal expressing counterparts. In contrast, cells containing elevated amount of SN were less vulnerable to classical apoptotic stressors than wild type cells. In addition, SN overexpression is accompanied by altered phenotype, attenuated proliferation kinetics, increased neurite arborisation and decreased cell motility. Based on these results, the SN overexpressing cell lines may represent a good and effective in vitro model for Alzheimer's and Parkinson's disease.