Neuroprotective and anti-inflammatory effects of pioglitazone on Parkinson's disease: A comprehensive narrative review of clinical and experimental findings

Abstract: Parkinson's disease [PD] is a chronic and progressive neurological disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta [SNc]. The pathogenesis of PD is strongly related with mitochondrial dysfunction, oxidative stress, and neuroinflammation. This indicates that PD can be treated with anti-oxidative substitutes and anti-inflammatory compounds. The neuroprotective and anti-inflammatory effects of peroxisome proliferator-activated receptor γ [PPAR-γ] agonists decrease cell death and halt the increase in neurodegeneration, which is why they have been given a lot of importance in research. Antidiabetic and anti-inflammatory effects have been observed to be generated by pioglitazone [PG], a selective peroxisome proliferator-activated receptor γ [PPAR-γ] agonist that regulates neural plasticity in various neurodegenerative disorders. The neuroprotective and anti-inflammatory effects of PG are assessed in this article. It was found that the patients with DM who received PG treatment were noticeably at a lower risk of PD. However, some clinical studies have not proven a strong link between the therapeutic effects of PG on PD. As per suggestions of preclinical studies, the therapeutic effects of PG treatment include; increased life expectancy of neurons, decreased oxidative stress, halted microglial activity, lower inflammation [reduced NF-κB, COX-2, and iNOS], reduced mitochondrial dysfunction, rise in motor function [motor agility] and non-motor function [lowered cognitive dysfunction]. In conclusion, we determined that PG exerts neuroprotective and anti-inflammatory effects in PD models and it can be considered a potential therapeutic candidate for PD.