The Molecular Impact of Glucosylceramidase Beta 1 (Gba1) in Parkinson ’s Disease: a New Genetic State of the Art

AbstractParkinson ’s disease (PD) is a neurodegenerative disorder affecting 2–3% of those aged over 65, characterized by motor symptoms like slow movement, tremors, and muscle rigidity, along with non-motor symptoms such as anxiety and dementia. Lewy bodies, clumps of misfolded proteins, contribute to neuron loss in PD. Mutations in theGBA1 gene are considered the primary genetic risk factor of PD.GBA1 mutations result in decreased activity of the lysosomal enzyme glucocerebrosidase (GCase) resulting in α-synuclein accumulation. We know that α-synuclein aggregation, lysosomal dysfunction, and endoplasmic reticulum disturbance are recognized factors to PD susceptibility; however, the molecular mechanisms connectingGBA1 gene mutations to increased PD risk remain partly unknown. Thus, in this narrative review conducted according to a systematic review method, we aimed to present the main contributions arising from the molecular impact of theGBA1 gene to the pathogenesis of PD providing new insights into potential impacts for advances in the clinical care of people with PD, a neurological disorder that has contributed to the substantial increase in the global burden of disease accentuated by the aging population. In summary, this narrative review highlights the multifaceted impact ofGBA1 mutations in PD, exploring their role in clinical manifestations, genetic predispositions, and molecular mechanisms. The review emphasizes the importance ofGBA1 mutations in both motor and ...
Source: Molecular Neurobiology - Category: Neurology Source Type: research