Food derived SIRT1 activator: a deacetylation-driven new way to fight neurodegenerative diseases

The primary characteristics of neurodegenerative diseases (NDs) are cognitive, motor and other dysfunctions resulting from the progressive loss of neurons, and the major mechanisms of NDs include abnormal aggregation of cytotoxic proteins, mitochondrial dysfunction, oxidative stress, and neuroinflammation. SIRT1 is a critical NAD+-dependent deacetylase and participates in widespread physiological processes, including energy metabolism, inflammation, and oxidation, which regulates the activity and function of multiple substrate proteins, thereby affecting intracellular signaling to ameliorate NDs. The signaling pathways involved in deacetylase SIRT1 mainly include the activation of AMPK, Akt and Nrf2 signals and the inhibition of NF-κB and NLRP3 inflammasome pathways, thereby alleviating mitochondrial dysfunction, oxidative stress, and neuroinflammation in NDs. Besides, microRNAs can adjust the activity of deacetylase SIRT1 to modulate the acetylation level of key molecular signals that influence the oxidative stress and neuroinflammation status in NDs. Notably, increasing evidence reveals natural food-derived deacetylase SIRT1 activators exhibit potential to fight NDs. This review primarily focuses on the role and underlying mechanism of SIRT1 on NDs, as well as the regulation of SIRT1 by microRNAs in NDs, and reveals the therapeutic effects of food sourced SIRT1 activators, especially bioactive ingredients from medicine food homology, so as to discover deacetylation-driven new therapeutic strategies for NDs.