Diabetic signature on Parkinson’s disease: Insights into pathophysiology and therapeutic repurposing

Abstract Parkinson’s disease (PD) and type 2 diabetes mellitus (T2DM) are among the most prevalent age-related neurodegenerative and metabolic disorders, respectively. Although genetic predisposition makes an individual susceptible to these conditions, environmental factors contribute to disease progression. This review aims to understand the shared pathophysiological mechanisms linking PD and T2DM and to explore the therapeutic repurposing of antidiabetic medication for the management of PD. A literature search using various databases was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines to select articles for this review. Several molecular pathogenic mechanisms—such as misfolded protein aggregation, mitochondrial dysfunction, oxidative stress, chronic inflammation, and gut microbiota dysbiosis—are common to both conditions. T2DM is associated with a higher incidence of PD, prompting the question of whether insulin resistance and chronic inflammation exacerbate neurodegenerative processes. In light of the common mechanistic links in pathogenesis, the therapeutic repurposing of antidiabetic agents offers a promising strategy for the management of PD. For instance, glucagon-like peptide-1 receptor agonists, originally developed for T2DM, have been found to exhibit neuroprotective effects by enhancing insulin sensitivity, reducing neuroinflammation, and improving mitochondrial function. Additionally, several interventions aimed at restoring mitophagy and gut microbial balance may mitigate disease progression by addressing metabolic and neurodegenerative dysfunction. In conclusion, targeting shared pathological pathways through metabolic interventions may provide dual benefits, offering prospects for novel therapeutic strategies for PD while improving T2DM management.