Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes, cortical neurons and fibroblasts

被引：76

作者：

Braidy N. ^{[1
,2
]}

Gai W.-P. ^{[3
]}

Xu Y.H. ^{[2
,4
]}

Sachdev P. ^{[1
,5
]}

Guillemin G.J. ^{[6
,7
]}

Jiang X.-M. ^{[8
]}

Ballard J.W.O. ^{[9
]}

Horan M.P. ^{[9
]}

Fang Z.M. ^{[8
]}

Chong B.H. ^{[8
]}

Chan D.K.Y. ^{[2
,3
,10
]}

机构：

[1] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney

[2] Aged Care and Rehabilitation, Bankstown-Lidcombe Hospital, Sydney

[3] Department of Human Physiology and Centre for Neuroscience, Flinders University School of Medicine, Adelaide

[4] Faculty of Medicine, University of New South Wales, Sydney

[5] Neuropsychiatric Institute, Prince of Wales Hospital, Sydney

[6] School of Medical Sciences, University of New South Wales, Sydney

[7] St Vincent's Centre for Applied Medical Research, Sydney

[8] St George Clinical School, University of New South Wales and St George Hospital, Sydney

[9] School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney

[10] Aged Care and Rehabilitation Unit, Bankstown-Lidcombe Hospital, Bankstown, 2031, NSW, Eldridge Road

来源：

Translational Neurodegeneration | / 2卷 / 1期

基金：

英国医学研究理事会;

关键词：

Alpha-synuclein; Astrocytes; Fibroblasts; Mitochondria; Neurons;

D O I：

10.1186/2047-9158-2-20

中图分类号：

学科分类号：

摘要：

The accumulation and aggregation of alpha-synuclein (α-syn) in several tissue including the brain is a major pathological hallmark in Parkinson's disease (PD). In this study, we show that α-syn can be taken up by primary human cortical neurons, astrocytes and skin-derived fibroblasts in vitro. Our findings that brain and peripheral cells exposed to α-syn can lead to impaired mitochondrial function, leading to cellular degeneration and cell death, provides additional evidence for the involvement of mitochondrial dysfunction as a mechanism of toxicity of α-syn in human cells. © 2013 Braidy et al.; licensee BioMed Central Ltd.

引用

共 41 条

[1]

Fahn S., Sulzer D., Neurodegeneration and neuroprotection in Parkinson disease, NeuroRx, 1, 1, pp. 139-154, (2004)

[2]

Keeney P., Xie J., Capaldi R., Benenett J., Parkinson's disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled, J Neurosci Res, 26, pp. 5256-5264, (2006)

[3]

Goetze O., Woitalla D., The role of MPTP in Parkinson's disease: connecting brain and gut?, Exp Neurol, 210, 2, pp. 281-285, (2008)

[4]

Halliday G., McCann H., Human-based studies on alpha-synuclein deposition and relationship to Parkinson's disease symptoms, Exp Neurol, 2008, pp. 12-21, (2008)

[5]

Lesage S., Brice A., Parkinson's Disease: from monogenic forms to genetic susceptibility factors, Hum Mol Genet, 18, (2009)

[6]

Spillantini M., Schmidt M., Lee V., Trojanowski J., Jakes R., Goerdert M., Alpha-synuclein in lewy bodies, Nature, 388, pp. 839-840, (1997)

[7]

Spillantini M.G., Crowther R.A., Jakes R., Hasegawa M., Goedert M., Alpha-synuclein in filamentous inclusions of lewy bodies from Parkinson's disease and dementia with lewy bodies, Proc Natl Acad Sci USA, 95, 11, pp. 6469-6473, (1998)

[8]

Wider C., Ross O.A., Nishioka K., Heckman M.G., Vilarino-Guell C., Jasinska-Myga B., Erketin-Taner N., Rademakers R., Graff-Radford N.R., Mash D.C., Papapetropoulos S., Duara R., Uchikado H., Wszolek Z.K., Farrer M.J., Dickson D.W., An evaluation of the impact of MAPT, SNCA and APOE on the burden of Alzheimer's and lewy body pathology, J Neurol Neurosurg Psychiatry, 83, 4, pp. 424-429, (2012)

[9]

Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R., Stenroos E.S., Chandrasekharappa S., Athanassiadou A., Papapetropoulos T., Johnson W.G., Lazzarini A.M., Duvoisin R.C., Di Iorio G., Golbe L.I., Nussbaum R.L., Mutation in the alpha-synuclein gene identified in families with Parkinson's disease, Science, 276, 5321, pp. 2045-2047, (1997)

[10]

Lee H.J., Patel S., Lee S.J., Intravesicular localization and exocytosis of alpha-synuclein and its aggregates, J Neurosci, 25, 25, pp. 6016-6024, (2005)

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