Crosstalk between presynaptic trafficking and autophagy in Parkinson's disease

Ping Yue Pan, Yingbo Zhu, Yuan Shen, Zhenyu Yue

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

Parkinson's disease (PD) is a debilitating neurodegenerative disorder that profoundly affects one's motor functions. The disease is characterized pathologically by denervation of dopaminergic (DAergic) nigrostriatal terminal and degeneration of DAergic neurons in the substantia nigra par compacta (SNpc); however, the precise molecular mechanism underlying disease pathogenesis remains poorly understood. Animal studies in both toxin-induced and genetic PD models suggest that presynaptic impairments may underlie the early stage of DA depletion and neurodegeneration (reviewed in Schirinzi, T., et al. 2016). Supporting this notion, human genetic studies and genomic analysis have identified an increasing number of PD risk variants that are associated with synaptic vesicle (SV) trafficking, regulation of synaptic function and autophagy/lysosomal system (Chang, D., et al. 2017, reviewed in Trinh, J. & Farrer, M. 2013; Singleton, A.B., et al. 2013). Although the precise mechanism for autophagy regulation in neurons is currently unclear, many studies demonstrate that autophagosomes form at the presynaptic terminal (Maday, S. & Holzbaur, E.L. 2014; Vanhauwaert, R., et al. 2017; reviewed in Yue, Z. 2007). Growing evidence has revealed overlapping genes involved in both SV recycling and autophagy, suggesting that the two membrane trafficking processes are inter-connected. Here we will review emergent evidence linking SV endocytic genes and autophagy genes at the presynaptic terminal. We will discuss their potential relevance to PD pathogenesis.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalNeurobiology of Disease
Volume122
DOIs
StatePublished - Feb 2019

Keywords

  • Autophagy
  • Endophilin
  • LRRK2
  • Parkinson's disease
  • Synaptic vesicle
  • Synaptojanin
  • a-synuclein

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