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

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.