A mechanistic narrative review of phytochemical enhancement of mitophagy in Parkinson’s disease: from PINK1/Parkin pathways to dopaminergic neuroprotection
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the loss of dopaminergic neurons, leading to manifestations of motor and non-motor dysfunctions. Mitochondrial dysfunction and impaired mitophagy contribute to the development and progression of PD, underlying dopaminergic neurodegeneration. The PINK1/Parkin signalling pathway is a cellular quality control systems contributing to dysfunctional mitochondria clearance. Its dysregulation is a canonical mechanism in both sporadic and familial PD pathogenesis. Phytochemicals have been reported to restore PINK1/Parkin signalling pathway and improve neuronal health by maintaining mitochondria homeostasis and mitophagy cascade. This review underscores the mechanisms of mitophagy modulation by phytochemicals through PINK1/Parkin signalling pathway and critically synthesize current and associated molecular, biochemical, and functional networks, reinforcing their significance to dopaminergic neuroprotection in PD experimental models. Studies published between 2010 and 2025 were comprehensively searched across google scholar and PubMed. Studies examining the effects of phytochemicals on mitochondrial function, mitophagy, and PINK1/Parkin signalling pathways in experimental PD models were the central focus of this review. Phytonutrient including baicalein, berberine, and resveratrol promote mitochondria homeostasis and dopaminergic neuroprotection by enhancing mitophagy through PINK1 stabilization, Parkin translocation and modulation of Nrf2 and SIRT1 pathways. Despite the promising neuroprotective effects of these phytonutrients, limitations including bioavailability, dosage, and experimental designs are major drawbacks necessitating standardized studies and clinical validation to make these findings translationally therapeutic to human with PD. Modulatory effects of phytochemicals on PINK1/Parkin-dependent mitophagy pathway provide a potential strategy for dopaminergic neuron protection in PD, providing insights into development of mitophagy-directed nutraceuticals and adjuvants.
Keywords: Parkinson’s disease, PINK1/Parkin, mitophagy, mitochondria homeostasis, phytochemicals, dopaminergic neuroprotection