Molecular mechanisms of α-synuclein and GBA1 in Parkinson’s disease

Iva Stojkovska, Dimitri Krainc, Joseph R. Mazzulli*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

47 Scopus citations


Parkinson’s disease (PD) is a neurodegenerative movement disorder characterized pathologically by the presence of Lewy bodies comprised of insoluble alpha (α)-synuclein. Pathological, clinical and genetic studies demonstrate that mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase) that is deficient in Gaucher’s disease, are important risk factors for the development of PD. The molecular mechanism for the association between these two diseases is not completely understood. We discuss several possible mechanisms that may lead to GBA1-related neuronal death and α-synuclein accumulation including disruptions in lipid metabolism, protein trafficking and impaired protein quality control mechanisms. Elucidating the mechanism between GCase and α-synuclein may provide insight into potential therapeutic pathways for PD and related synucleinopathies.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalCell and Tissue Research
Issue number1
StatePublished - Oct 24 2018


  • Alpha (α)-synuclein
  • Glucosylceramide
  • Lysosomal dysfunction
  • Neurodegeneration
  • Protein aggregation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology


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