Neurotoxicity Research

, Volume 25, Issue 2, pp 170–182

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 J. Guillemin
  • Xing-Mai Jiang
  • J. William O. Ballard
  • Martin P. Horan
  • Zhi Ming Fang
  • Beng H. Chong
  • Daniel Kam Yin Chan
Original Article

DOI: 10.1007/s12640-013-9420-5

Cite this article as:
Braidy, N., Gai, WP., Xu, Y.H. et al. Neurotox Res (2014) 25: 170. doi:10.1007/s12640-013-9420-5

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.

Keywords

Alpha-synucleinParkinson’s diseaseEndocytosisMitochondriaNAD+

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nady Braidy
    • 1
    • 2
  • Wei-Ping Gai
    • 3
  • Ying Hua Xu
    • 2
    • 4
  • Perminder Sachdev
    • 1
    • 5
  • Gilles J. Guillemin
    • 6
    • 7
  • Xing-Mai Jiang
    • 8
    • 10
  • J. William O. Ballard
    • 9
  • Martin P. Horan
    • 9
  • Zhi Ming Fang
    • 8
    • 10
  • Beng H. Chong
    • 8
    • 10
  • Daniel Kam Yin Chan
    • 2
    • 4
  1. 1.Centre for Healthy Brain Ageing, School of PsychiatryUniversity of New South WalesSydneyAustralia
  2. 2.Aged Care and Rehabilitation UnitBankstown-Lidcombe HospitalBankstownAustralia
  3. 3.Department of Human Physiology and Centre for NeuroscienceFlinders University School of MedicineAdelaideAustralia
  4. 4.Faculty of MedicineUniversity of New South WalesSydneyAustralia
  5. 5.Neuropsychiatric InstitutePrince of Wales HospitalSydneyAustralia
  6. 6.School of Medical SciencesUniversity of New South WalesSydneyAustralia
  7. 7.St Vincent’s Centre for Applied Medical ResearchSydneyAustralia
  8. 8.St George Clinical School, University of New South WalesSydneyAustralia
  9. 9.School of Biotechnology and Biomolecular SciencesUniversity of New South WalesSydneyAustralia
  10. 10.St George HospitalSydneyAustralia