Alpha-Synuclein Transmission and Mitochondrial Toxicity in Primary Human Foetal Enteric Neurons In Vitro

作者：Braidy Nady; Gai Wei Ping; Xu Ying Hua; Sachdev Perminder; Guillemin Gilles J; Jiang Xing Mai; Ballard J William O; Horan Martin P; Fang Zhi Ming; Chong Beng H; Chan Daniel Kam Yin^*

来源：Neurotoxicity Research, 2014, 25(2): 170-182.

DOI：10.1007/s12640-013-9420-5

• Alpha-synuclein
• Parkinson%26apos
• s disease
• Endocytosis
• Mitochondria
• NAD(+)

Parkinson%26apos;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%26apos;s hypothesis and the aetiology of PD.

• 出版日期2014-2