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Mov Disord. 2019 Jan;34(1):9-21. doi: 10.1002/mds.27583. Epub 2018 Dec 27.

Glucocerebrosidase mutations and synucleinopathies: Toward a model of precision medicine.

Author information

1
Laboratory of Functional Neurochemistry, IRCCS Mondino Foundation, Pavia, Italy.
2
Parkinson Institute, ASST Gaetano Pini-CTO, Milan, Italy.
3
Department of Clinical Neurosciences, Institute of Neurology, University College London, Hampstead, UK.
4
Institute of Translational and Stratified Medicine, Plymouth University Peninsula School of Medicine, Plymouth, UK.
5
Programa de Neurociencias, Fundación para la Investigación Médica Aplicada (FIMA), Universidad de Navarra, Pamplona, Spain.
6
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CiberNed), Madrid, Spain.
7
Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.

Abstract

Glucocerebrosidase is a lysosomal enzyme. The characterization of a direct link between mutations in the gene coding for glucocerebrosidase (GBA1) with the development of Parkinson's disease and dementia with Lewy bodies has heightened interest in this enzyme. Although the mechanisms through which glucocerebrosidase regulates the homeostasis of α-synuclein remains poorly understood, the identification of reduced glucocerebrosidase activity in the brains of patients with PD and dementia with Lewy bodies has paved the way for the development of novel therapeutic strategies directed at enhancing glucocerebrosidase activity and reducing α-synuclein burden, thereby slowing down or even preventing neuronal death. Here we reviewed the current literature relating to the mechanisms underlying the cross talk between glucocerebrosidase and α-synuclein, the GBA1 mutation-associated clinical phenotypes, and ongoing therapeutic approaches targeting glucocerebrosidase.

KEYWORDS:

GBA1; GCase; Lewy bodies; Parkinson's disease; α-synuclein

PMID:
30589955
DOI:
10.1002/mds.27583

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