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 theSNCAgene encoding alpha-synuclein(α-Syn), as well as other genes such as leucine-rich repeat kinase 2(LRRK2), ParkinRBR 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)andSNCAthat 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, withSNCAmutations exacerbatingα-Synaggregation and disease severity.Alpha-synucleinlevels in skin, serum, cerebrospinal fluid, and plasma distinguish PD patients from healthy patients, demonstrating biomarker potential for diagnosis and therapeutic strategies. Furthermore,α-Syn'spresence in neural crest-derived tissues from PD patients and melanoma patients suggests shared pathophysiological features. Ongoing research intoSNCAandα-Synis crucial for advancing diagnostics and therapeutics for neurodegenerative diseases.
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