Flavonoids modulate AMPK/PGC-1α and interconnected pathways toward potential neuroprotective activities

As progressive, chronic, incurable and common reasons for disability and death, neurodegenerative diseases (NDDs) are significant threats to human health. Besides, the increasing prevalence of neuronal gradual degeneration and death during NDDs has made them a global concern. Since yet, no effective treatment has been developed to combat multiple dysregulated pathways/mediators and related complications in NDDs. Therefore, there is an urgent need to create influential and multi-target factors to combat neuronal damages. Accordingly, the plant kingdom has drawn a bright future. Among natural entities, flavonoids are considered a rich source of drug discovery and development with potential biological and medicinal activities. Growing studies have reported multiple dysregulated pathways in NDDs, which among those mediator AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) play critical roles. In this line, critical role of flavonoids in the upregulation of AMPK/PGC-1α pathway seems to pave the road in the treatment of Alzheimer's disease (AD), Parkinson's disease (PD), aging, central nervous system (brain/spinal cord) damages, stroke, and other NDDs. In the present study, the regulatory role of flavonoids in managing various NDDs has been shown to pass through AMPK/PGC-1α signaling pathway.