Genetics and Pathogenesis of Parkinson's Syndrome

Hui Ye, Laurie A. Robak, Meigen Yu, Matthew Cykowski, Joshua M. Shulman

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations


Parkinson's disease (PD) is clinically, pathologically, and genetically heterogeneous, resisting distillation to a single, cohesive disorder. Instead, each affected individual develops a virtually unique form of Parkinson's syndrome. Clinical manifestations consist of variable motor and nonmotor features, and myriad overlaps are recognized with other neurodegenerative conditions. Although most commonly characterized by alpha-synuclein protein pathology throughout the central and peripheral nervous systems, the distribution varies and other pathologies commonly modify PD or trigger similar manifestations. Nearly all PD is genetically influenced. More than 100 genes or genetic loci have been identified, and most cases likely arise from interactions among many common and rare genetic variants. Despite its complex architecture, insights from experimental genetic dissection coalesce to reveal unifying biological themes, including synaptic, lysosomal, mitochondrial, andimmune-mediated mechanisms of pathogenesis. This emerging understanding of Parkinson's syndrome, coupled with advances in biomarkers and targeted therapies, presages successful precision medicine strategies.

Original languageEnglish (US)
Pages (from-to)95-121
Number of pages27
JournalAnnual Review of Pathology: Mechanisms of Disease
StatePublished - Jan 24 2023


  • GBA
  • LRRK2
  • Parkinsons disease
  • alpha-synuclein
  • functional genomics
  • heterogeneity
  • lysosome
  • mitochondria
  • oligogenic
  • parkinsonism
  • synapse

ASJC Scopus subject areas

  • Medicine(all)


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