期刊
NEUROTOXICITY RESEARCH
卷 25, 期 2, 页码 170-182出版社
SPRINGER
DOI: 10.1007/s12640-013-9420-5
关键词
Alpha-synuclein; Parkinson's disease; Endocytosis; Mitochondria; NAD(+)
资金
- UNSW Faculty of Medicine Research Grant
- Alzheimer's Australia Viertel Foundation
- NHMRC Early Career Postdoctoral Research Grant at the University of New South Wales
- Alzheimer's Association [IIRG-08-89545]
- Rebecca Cooper foundation (Australia)
Parkinson's disease (PD) is a multicentred neurodegenerative disorder characterised by the accumulation and aggregation of alpha-synuclein (alpha-syn) in several parts of the central nervous system. However, it is well established that PD can generate symptoms of constipation and other gastrointestinal problems and alpha-syn containing lesions have been identified in intestinal nerve cells. In this study, we show that alpha-syn can be taken up and accumulate in primary human foetal enteric neurons from the gastrointestinal tract and can be transferred between foetal enteric neurons. Impaired proteosomal/lysosomal degradation can promote the uptake and accumulation of alpha-syn in enteric neurons. Enteric neurons exposed to alpha-syn can also lead to impaired mitochondrial complex I activity, reduced mitochondrial function, and NAD(+) depletion culminating in cell death via energy restriction. These findings demonstrate neuron-to-neuron transmission of alpha-syn in enteric neurons, providing renewed evidence for Braak's hypothesis and the aetiology of PD.
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