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Cross-talks among GBA mutations,glucocerebrosidase,and a-synuclein in 66/4-associated Parkinson's disease and their targeted therapeutic approaches:a comprehensive review

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Translational Neurodegeneration 2021年第1期10卷 27-39页

作者： Tapan Behl Gagandeep Kaur Ovidiu Fratila camelia buhas Claudia Teodora Judea-Pusta Nicoleta Negrut Cristiana Bustea Simona Bungau Chitkara College of Pharmacy Chitkara UniversityRajpuraPunjabIndia Departm ent of Medical Disciplines Faculty of Medicine and PharmacyUniversity of OradeaOradeaRomania Department of Morphological Disciplines Faculty of Medicine and PharmacyUniversity of OradeaOradeaBihor CountyRomania Departm ent of Psycho-Neuroscience and Recovery Faculty of Medicine and PharmacyUniversity of OradeaOradeaRomania Department of Preclinical Disciplines Faculty of Medicine and PharmacyUniversity of OradeaOradeaRomania Department of Pharmacy Faculty of Medicine and PharmacyUniversity of OradeaOradeaRomania

Current therapies for Parkinson's disease(PD)are palliative,of which the levodopa/carbidopa therapy remains the primary choice but is unable to modulate the progression of *** to the complication of such a multifactorial disorder and significant limitations of the therapy,numerous genetic approaches have been proved effective in finding out genes and mechanisms implicated in this *** the observation of a higher frequency of PD in Gaucher's disease(GD),a lysosomal storage condition,mutations of glycosylceramidase beta(GBA)encoding glucocerebrosidase(GCase)have been shown to be involved and have been explored in the context of *** mutations are the most common genetic risk factor of *** studies have revealed the relationships between PD and GM gene mutations,facilitating a better understanding of this *** hypotheses delineate that the pathological mutations of GBA minimize the enzymatic activity of GCase,which affects the proliferation and clearance of α-synuclein;this affects the lysosomal homeostasis,exacerbating the endoplasmic reticulum stress or encouraging the mitochondrial *** of the pathological mechanisms underlying the GM-associated parkinsonism(GBA+PD)advances our understanding of *** review based on current literature aims to elucidate various genetic and clinical characteristics correlated with GBA mutations and to identify the numerous pathological processes underlying GBA+*** also delineate the therapeutic strategies to interfere with the mutant GCase function for further improvement of the related asynuclein-GCase ***,the various therapeutic approaches such as gene therapy,chaperone proteins,and histone deacetylase inhibitors for the treatment of GBA+PD are discussed.

关键词： Parkinson's disease Glycosylceramidase Glucocerebrosidase Gaucher's disease Mutations α-Synuclein

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