Bioinformatics-Guided Drug Repurposing for Precision Management of Parkinson’s Disease: Targeting the LRRK2 G2019S

Parkinson's disease affects over 2-3% of individuals aged 65 and above, with Leucine-Rich Repeat Kinase 2 (LRRK2) playing a fundamental role in its pathogenesis. The G2019S mutation in LRRK2 upsurges kinase activity, targeting molecules concomitant with apoptosis, and is a mutual genetic cause. LRRK2's involvement in various neurodegenerative diseases and cancer highlights its probable as a therapeutic target. Abnormal LRRK2 activity affects mitochondrial function, autophagy, and neurological inflammation. Targeting LRRK2 offers an exclusive opportunity to address multiple pathways in Parkinson's development. Screening 3,674 FDA-approved drugs for their affinity to LRRK2 identified Ponatinib, a tyrosine kinase inhibitor initially developed for leukemia treatment, as a favourable candidate. Ponatinib's ability to modify LRRK2 activity and potentially offer neuroprotection makes it an attractive option for Parkinson's prophylaxis. Physicochemical analysis via SWISS-ADME supports Ponatinib's suitability. This analysis suggests Ponatinib's repositioning as a PD prophylactic by targeting LRRK2. Further studies are necessitated to investigate its efficacy in preventing Parkinson's disease.