Abstract
Neurological disorders, including neurodegenerative diseases, have a significant negative impact on both patients and society at large. Since the prevalence of most of these disorders increases with age, the consequences for our aging population are only going to grow. It is now acknowledged that neurological disorders are multi-factorial involving disruptions in multiple cellular systems. While each disorder has specific initiating mechanisms and pathologies, certain common pathways appear to be involved in most, if not all, neurological disorders. Thus, it is becoming increasingly important to identify compounds that can modulate the multiple pathways that contribute to disease development or progression. One of these compounds is the flavonol fisetin. Fisetin has now been shown in preclinical models to be effective at preventing the development and/or progression of multiple neurological disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, stroke (both ischemic and hemorrhagic) and traumatic brain injury as well as to reduce age-associated changes in the brain. These beneficial effects stem from its actions on multiple pathways associated with the different neurological disorders. These actions include its well characterized anti-inflammatory and anti-oxidant effects as well as more recently described effects on the regulated cell death oxytosis/ferroptosis pathway, the gut microbiome and its senolytic activity. Therefore, the growing body of pre-clinical data, along with fisetin's ability to modulate a large number of pathways associated with brain dysfunction, strongly suggest that it would be worthwhile to pursue its therapeutic effects in humans.