Alpha-synuclein toxicity in the early secretory pathway: How it drives neurodegeneration in parkinsons disease

Ting Wang, Jesse C. Hay

Research output: Contribution to journalShort surveypeer-review

Abstract

Alpha-synuclein is a predominant player in the pathogenesis of Parkinson's Disease. However, despite extensive study for two decades, its physiological and pathological mechanisms remain poorly understood. Alpha-synuclein forms a perplexing web of interactions with lipids, trafficking machinery, and other regulatory factors. One emerging consensus is that synaptic vesicles are likely the functional site for alpha-synuclein, where it appears to facilitate vesicle docking and fusion. On the other hand, the dysfunctions of alpha-synuclein are more dispersed and numerous; when mutated or over-expressed, alpha-synuclein affects several membrane trafficking and stress pathways, including exocytosis, ER-to-Golgi transport, ER stress, Golgi homeostasis, endocytosis, autophagy, oxidative stress, and others. Here we examine recent developments in alpha-synuclein's toxicity in the early secretory pathway placed in the context of emerging themes from other affected pathways to help illuminate its underlying pathogenic mechanisms in neurodegeneration.

Original languageEnglish
Article number433
JournalFrontiers in Neuroscience
Volume9
Issue numberNOV
DOIs
StatePublished - 2015

Keywords

  • Alpha-synuclein
  • ER stress response
  • ER to golgi transport
  • Golgi
  • LRRK2
  • Neurodegenerative diseases
  • Parkinson disease
  • Vesicle trafficking

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