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

Nady Braidy, Wei-Ping Gai, Ying Hua Xu, Perminder Sachdev, Gilles Guillemin, Xing-Mai Jiang, J. Ballard, Martin Horan, Zhi Ming Fang, B Chong, Daniel Chan

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)

    Abstract

    Parkinson's disease (PD) is a multicentred neurodegenerative disorder characterised by the accumulation and aggregation of alpha-synuclein (α-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 α-syn containing lesions have been identified in intestinal nerve cells. In this study, we show that α-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 α-syn in enteric neurons. Enteric neurons exposed to α-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 α-syn in enteric neurons, providing renewed evidence for Braak's hypothesis and the aetiology of PD.

    Original languageEnglish
    Pages (from-to)170-182
    Number of pages13
    JournalNeurotoxicity Research
    Volume25
    Issue number2
    DOIs
    Publication statusPublished - 2014

    Keywords

    • Alpha-synuclein
    • Endocytosis
    • Mitochondria
    • NAD
    • Parkinson's disease

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