Targeting PI3K/Akt/mTOR with fisetin mechanistic and therapeutics insights for Parkinson’s disease

Parkinson’s disease (PD) is a developing neurodegenerative illness marked by oxidative stress, neuroinflammation, mitochondrial dysfunction, and lack of dopaminergic neurons. The PI3K/Akt/mTOR pathways significantly affect all synaptic plasticity, autophagy regulation, and neuronal survival. A dietary flavonoid present in a variety of vegetables and fruits, fisetin has more anti-inflammatory, antioxidant and anti-apoptotic properties. According to new research, fisetin may be able to alter PI3K/Akt/mTOR signaling in experimental PD models, restoring autophagic flow, lowering oxidative stress, and preventing dopaminergic cell death. This review aims to provide a comprehensive overview of the molecular and therapeutic significance of fisetin in Parkinson’s disease models and to clarify how it modulates the PI3K/Akt/mTOR signaling cascade. Additionally, it evaluates the available data, research gaps, and potential for future translation. A comprehensive review of the literature was carried out using relevant keywords from a number of scientific source including Scopus, Web of science, PubMed, Google Scholar. Studies on the fisetin, Parkinson’s disease models, PI3K/Akt/mTOR signaling, and in vitro, in vivo and molecular docking data. The outcomes combined to emphasise therapeutic results and molecular pathways. Fisetin improves neuronal survival in Parkinson’s disease models by activating PI3K/Akt, controlling mTOR, boosting autophagy, and lowering oxidative stress, inflammation, and α-synuclein accumulation. Fisetin significant neuroprotective potential for Parkinson’s disease, supported by its modulation of the PI3K/Akt/mTOR pathway, which promotes more preclinical and clinical research.