Objective: This study aimed to investigate SNCA gene alterations alongside oxidative stress and mitochondrial dysfunction in early-onset PD (EOPD) and late-onset PD (LOPD) subjects from the Punjab population of India.

Background: Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by progressive dopaminergic neuronal loss, with oxidative stress, mitochondrial dysfunction, and impaired energy metabolism playing central roles in its pathophysiology. Alpha-synuclein (SNCA) is a key molecular contributor to PD, influencing mitochondrial integrity and redox homeostasis.

Method: A total of 56 clinically diagnosed PD patients (LOPD and EOPD) were recruited from AIIMS Bathinda, along with age- and sex-matched healthy controls. Clinical and demographic parameters were documented. SNCA gene expression analysis and Sanger sequencing were performed to assess molecular alterations. Biochemical evaluations included free radical scavenging capacity, antioxidant enzyme activities (superoxide dismutase [SOD] and catalase [CAT]), and mitochondrial membrane potential (MMP). Statistical analyses were conducted to compare PD subgroups and controls.

Results: PD patients exhibited a significant upregulation of SNCA expression compared to controls (p < 0.0001), with Sanger sequencing identifying functionally relevant SNCA variants. Mitochondrial assessments revealed significant depolarization and reduced MMP in PD subjects (p < 0.0001). Oxidative stress analysis demonstrated marked redox imbalance, particularly in LOPD patients, characterized by elevated hydroxyl radical scavenging activity (p < 0.0001), reduced SOD activity, and increased CAT levels (p < 0.005).

Conclusion: This study highlights the critical interplay between SNCA dysregulation, oxidative stress, and mitochondrial depolarization, in the pathophysiology of PD. The biochemical alterations were more pronounced in LOPD subjects, suggesting greater mitochondrial vulnerability with advancing disease onset. These findings support the potential of SNCA-linked oxidative and mitochondrial markers as valuable indicators for disease monitoring and therapeutic stratification.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/snca-dysregulation-drives-oxidative-stress-and-mitochondrial-dysfunction-in-parkinsons-disease-evidence-from-a-punjab-cohort/