Therapeutic innovation through drug repurposing: A multidimensional approach toward treating Parkinson's disease

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease, primarily affecting the aging population. Despite the introduction of levodopa in the 1960s and significant progress in managing PD symptoms, no treatment has yet demonstrated neuroprotective efficacy. The complexity and multifactorial nature of PD continue to present substantial therapeutic challenges, prompting researchers to explore alternative approaches such as drug repurposing. This strategy offers a time- and cost-efficient route to drug development. Recent efforts have focused on repurposing agents originally developed for metabolic and other non-neurological disorders. Ongoing research is actively investigating several repurposed drugs originally intended for different conditions, including anti-hypertensives (isradipine, dexmedetomidine), anti-asthmatics (montelukast), phosphodiesterase5 inhibitors (sildenafil), antimicrobials (rifaximin), and various CNS-active agents (aripiprazole, escitalopram, paroxetine, venlafaxine, duloxetine, caffeine). While drug repurposing holds considerable promise, comprehensive preclinical and clinical studies are essential to validate these candidates for PD-specific therapeutic applications. This review aims to provide an in-depth overview of PD, encompassing its pathological and molecular characteristics, and to critically evaluate the current landscape of drug repurposing strategies to develop effective therapies for PD.