Abstract

FRONTIER IN PARKINSON’S DISEASE: UNITING GENE–ENVIRONMENT BIOLOGY WITH EMERGING BIOMARKERS, ADAPTIVE NEUROMODULATION, AND REGENERATIVE APPROACHES

*Yeshwanth Pranav, Kasthuri, Balaji, Madhan Kumar, Niranjan, Syed Mansur

ABSTRACT

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra, producing a wide range of motor and non-motor symptoms. As its global prevalence continues to rise, PD has become a major public health concern. This review summarizes recent findings from 2020–2025 on epidemiology, risk factors, gene - environment interactions, and key pathological mechanisms, including α-synuclein aggregation, mitochondrial dysfunction, and impaired lysosomal activity. Advances in diagnostic biomarkers - such as CSF seed-amplification assays, neurofilament markers, and neuroimaging are highlighted alongside current therapeutic approaches like deep brain stimulation, dopaminergic infusion therapies, and multidisciplinary rehabilitation. Emerging disease-modifying strategies, including gene therapy, stem-cell–based approaches, GBA/LRRK2-targeted treatments, and microbiome-focused interventions, reflect promising directions for future care. Overall, the review emphasizes early diagnosis and personalized treatment to improve patient outcomes.

Keywords: Parkinson’s disease, Neurodegeneration, ?-synuclein aggregation, Mitochondrial dysfunction, Lysosomal impairment, Diagnostic biomarkers, Deep brain stimulation, Dopaminergic therapies, Disease-modifying strategies, Gene and stem-cell therapies, Microbiome