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

Iva Stojkovska, Dimitri Krainc, Joe Mazzulli*

*Corresponding author for this work

Research output: Contribution to journalReview article

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalCell and Tissue Research
Volume373
Issue number1
DOIs
StatePublished - Oct 24 2018

Fingerprint

Synucleins
Glucosylceramidase
Parkinson Disease
Lewy Bodies
Gaucher Disease
alpha-Synuclein
Movement Disorders
Protein Transport
Lipid Metabolism
Neurodegenerative Diseases
Quality Control
Mutation
Enzymes
Genes
Proteins
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

Cite this

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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.",
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Molecular mechanisms of α-synuclein and GBA1 in Parkinson’s disease. / Stojkovska, Iva; Krainc, Dimitri; Mazzulli, Joe.

In: Cell and Tissue Research, Vol. 373, No. 1, 24.10.2018, p. 51-60.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Molecular mechanisms of α-synuclein and GBA1 in Parkinson’s disease

AU - Stojkovska, Iva

AU - Krainc, Dimitri

AU - Mazzulli, Joe

PY - 2018/10/24

Y1 - 2018/10/24

N2 - 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.

AB - 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.

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