Repurposing Saroglitazar for neurodegenerative disorders: insight into molecular signalling pathways and neuroprotective modulations.

Drug repurposing has emerged as a cost-efficient strategy for neurodegenerative disorders (NDDs), leveraging existing preclinical, safety, and tolerability data to identify therapeutic candidates. NDDs, including epilepsy, Parkinson's disease (PD), Alzheimer's disease (AD), and traumatic brain injury (TBI), are characterized by neuroinflammation, oxidative stress, and neuronal degeneration, with key signaling pathways such as HMGB1, TRPA1, NF-κB, MAPK, and PI3K/Akt-GSK3β playing pivotal roles in their pathogenesis. Given the established link between type 2 diabetes mellitus and neurodegeneration, Saroglitazar, a dual PPAR-α/γ agonist, holds promise in modulating insulin signaling, oxidative stress, neuroinflammation, and key pathways, including HMGB1, TRPA1, NF-κB, MAPK, and PI3K/Akt-GSK3β. This is the first comprehensive review to examine the effects of Saroglitazar in modulating multiple pathways associated with NDDs, thereby addressing existing gaps in the literature. The review explores the mechanistic interplay among these pathways and emphasizes the potential of Saroglitazar as a neuroprotective agent, highlighting the need for further studies to validate its clinical efficacy and disease-modifying capabilities in NDDs. All supporting data were obtained from peer-reviewed literature accessed via PubMed, Web of Science, and Scopus.