GBA1 mutations: Prospects for exosomal biomarkers in α-synuclein pathologies

Parker H. Johnson, Neal J. Weinreb, James C. Cloyd, Paul J. Tuite, Reena V. Kartha

Research output: Contribution to journalReview article


The discovery that patients with Gaucher Disease (GD), a rare lysosomal storage disorder, were developing symptoms similar to Parkinson's disease (PD) led to investigation of the relationship between the two seemingly unrelated pathologies. GD, an autosomal recessive disorder, is the result of a biallelic mutation in the gene GBA1, which encodes for the enzyme glucocerebrosidase (GCase). Since the observation of its relation to PD, GBA1 mutations have become recognized as the most common genetic risk factor for development of synucleinopathies such as PD and dementia with Lewy bodies. Although the exact mechanism by which GBA1 mutations promote PD is unknown, current understanding suggests that impaired GCase inhibits lysosomal activity and decreases the overall ability of the cell to degrade proteins, specifically the neuronal protein α-synuclein. Decreased elimination of α-synuclein can lead to its abnormal accumulation and aggregation, an important component of PD development. Further understanding of how decreased GCase activity increases risk for α-synuclein pathology can assist with the development of clinical biomarkers for early detection of synucleinopathies, as well as promote novel treatments tailored for people with a GBA1 mutation. Historically, α-synuclein has not been a reliable biomarker for PD. However, recent research on α-synuclein content within exosomes, which are small vesicles released by cells that carry specific cellular cargo, has yielded encouraging results. Moreover, decreased GCase activity has been shown to influence exosomal contents. Exosomes have emerged as a promising new avenue for the identification of novel biomarkers and therapeutic targets aimed at improving neuronal GCase function and limiting the development of synucleinopathies.

Original languageEnglish (US)
Pages (from-to)35-46
Number of pages12
JournalMolecular Genetics and Metabolism
Issue number2
StatePublished - Feb 2020


  • Alpha-synuclein
  • Biomarker
  • Carriers
  • Exosomes
  • GBA1
  • Gaucher disease

PubMed: MeSH publication types

  • Journal Article
  • Review
  • Research Support, N.I.H., Extramural

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