Regulation of mitophagy and mitochondrial function: Natural compounds as potential therapeutic strategies for Parkinson's disease

Abstract Mitochondrial damage is associated with the development of Parkinson's disease (PD), indicating that mitochondrial‐targeted treatments could hold promise as disease‐modifying approaches for PD. Notably, natural compounds have demonstrated the ability to modulate mitochondrial‐related processes. In this review article, we discussed the possible neuroprotective mechanisms of natural compounds against PD in modulating mitophagy and mitochondrial function. A comprehensive literature search on natural compounds related to the treatment of PD by regulating mitophagy and mitochondrial function was conducted from PubMed, Web of Science and Chinese National Knowledge Infrastructure databases from their inception until April 2023. We summarize recent advancements in mitophagy's molecular mechanisms, including upstream and downstream processes, and its relationship with PD‐related genes or proteins. Importantly, we highlight how natural compounds can therapeutically regulate various mitochondrial processes through multiple targets and pathways to alleviate oxidative stress, neuroinflammation, Lewy's body aggregation and apoptosis, which are key contributors to PD pathogenesis. Unlike the single‐target strategy of modern medicine, natural compounds provide neuroprotection against PD by modulating various mitochondrial‐related processes, including ameliorating mitophagy by targeting the PINK1/parkin pathway, the NIX/BNIP3 pathway, and autophagosome formation (i.e., LC3 and p62). Given the prevalence of mitochondrial damage in various neurodegenerative diseases, exploring the exact mechanism of natural compounds on mitophagy and mitochondrial dysfunction could shed light on the development of highly effective disease‐modifying or adjuvant therapies targeting PD and other neurodegenerative disorders.