Alpha-Synuclein Transmission and Mitochondrial Toxicity in Primary Human Foetal Enteric Neurons In Vitro
Alpha-Synuclein Transmission and Mitochondrial Toxicity in Primary Human Foetal Enteric Neurons In Vitro
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DOI：
10.1007/s12640-013-9420-5
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发表时间：
2014-02-01
影响因子：
3.7
通讯作者：
Chan, Daniel Kam Yin
中科院分区：
文献类型：
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作者：
Braidy, Nady;Gai, Wei-Ping;Chan, Daniel Kam Yin
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.
