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Home > Students & health professionals > Books & Publications > Publications > Parkinsonisms and Glucocerebrosidase Deficiency: A Comprehensive Review for (...)

Parkinsonisms and Glucocerebrosidase Deficiency: A Comprehensive Review for Molecular and Cellular Mechanism of Glucocerebrosidase Deficiency

Emilia M. Gatto et al. Brain Sci. 2019, 9, 30

Abstract: In the last years, lysosomal storage diseases appear as a bridge of knowledge between
rare genetic inborn metabolic disorders and neurodegenerative diseases such as Parkinson’s
disease (PD) or frontotemporal dementia. Epidemiological studies helped promote research in the
field that continues to improve our understanding of the link between mutations in the
glucocerebrosidase (GBA) gene and PD. We conducted a review of this link, highlighting the
association in GBA mutation carriers and in Gaucher disease type 1 patients (GD type 1). A
comprehensive review of the literature from January 2008 to December 2018 was undertaken.
Relevance findings include: (1) There is a bidirectional interaction between GBA and α- synuclein
in protein homeostasis regulatory pathways involving the clearance of aggregated proteins. (2) The
link between GBA deficiency and PD appears not to be restricted to α–synuclein aggregates but
also involves Parkin and PINK1 mutations. (3) Other factors help explain this association, including
early and later endosomes and the lysosomal-associated membrane protein 2A (LAMP-2A)
involved in the chaperone-mediated autophagy (CMA). (4) The best knowledge allows researchers
to explore new therapeutic pathways alongside substrate reduction or enzyme replacement
Keywords: glucocerebrosidase; Parkinson’s disease; Gaucher disease