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

  • Iva Stojkovska
  • Dimitri Krainc
  • Joseph R. Mazzulli
Review

Abstract

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.

Keywords

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

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Iva Stojkovska
    • 1
  • Dimitri Krainc
    • 1
  • Joseph R. Mazzulli
    • 1
  1. 1.The Ken and Ruth Davee Department of NeurologyNorthwestern University Feinberg School of MedicineChicagoUSA

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