A Review on the Role of SNCA Gene in Neurodegenerative Diseases.

Research overview

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Gene variations significantly impact the development of neurodegenerative disorders, particularly Alzheimer's disease (AD) and Parkinson's disease (PD). In AD, which is marked by amyloid-beta (Aβ) plaques and tau tangles, key genetic contributors such as amyloid beta precursor protein (APP), presenilin (PSEN1), and presenilin 2 (PSEN2) play a significant role in early-onset familial AD due to their influence on Aβ accumulation. PD, marked by dopaminergic neuron degeneration and Lewy body formation, is associated with mutations in the SNCA gene encoding alpha-synuclein (α-Syn), as well as other genes such as leucine-rich repeat kinase 2 (LRRK2), Parkin RBR E3 ubiquitin-protein ligase (PARK2), PTEN-induced kinase 1 (PINK1), and protein deglycase (DJ-1). Genome-wide association studies have identified genetic variants in apolipoprotein (APOE) and SNCA that increase disease risk. Alpha-synuclein, a protein involved in synaptic function, misfolds and aggregates into toxic forms in neurodegenerative diseases. Aggregates disrupt neuronal functions and propagate in a prion-like manner, with SNCA mutations exacerbating α-Syn aggregation and disease severity. Alpha-synuclein levels in skin, serum, cerebrospinal fluid, and plasma distinguish PD patients from healthy patients, demonstrating biomarker potential for diagnosis and therapeutic strategies. Furthermore, α-Syn's presence in neural crest-derived tissues from PD patients and melanoma patients suggests shared pathophysiological features. Ongoing research into SNCA and α-Syn is crucial for advancing diagnostics and therapeutics for neurodegenerative diseases.

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