Synaptic, Mitochondrial, and Lysosomal Dysfunction in Parkinson's Disease

Maria Nguyen, Yvette C. Wong, Daniel Ysselstein, Alex Severino, Dimitri Krainc*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

151 Scopus citations


The discovery of genetic forms of Parkinson's disease (PD) has highlighted the importance of the autophagy/lysosomal and mitochondrial/oxidative stress pathways in disease pathogenesis. However, recently identified PD-linked genes, including DNAJC6 (auxilin), SYNJ1 (synaptojanin 1), and the PD risk gene SH3GL2 (endophilin A1), have also highlighted disruptions in synaptic vesicle endocytosis (SVE) as a significant contributor to disease pathogenesis. Additionally, the roles of other PD genes such as LRRK2, PRKN, and VPS35 in the regulation of SVE are beginning to emerge. Here we discuss the recent work on the contribution of dysfunctional SVE to midbrain dopaminergic neurons’ selective vulnerability and highlight pathways that demonstrate the interplay of synaptic, mitochondrial, and lysosomal dysfunction in the pathogenesis of PD.

Original languageEnglish (US)
Pages (from-to)140-149
Number of pages10
JournalTrends in Neurosciences
Issue number2
StatePublished - Feb 2019


  • Parkinson's disease
  • genetics
  • oxidized dopamine
  • synaptic vesicle endocytosis
  • αSynuclein

ASJC Scopus subject areas

  • Neuroscience(all)


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