NEUROPROTECTIVE ROLE OF FISETIN IN THE TREATMENT AND PREVENTION OF ALZHEIMER'S DISEASE

Abstract Progressive neurodegeneration characterizes Alzheimer's disease (AD) which causes cognitive decline, synaptic dysfunction, oxidative stress, mitochondrial dysfunction, neuroinflammation, and neuronal death. The limited relief afforded by available therapies highlights the need for multifunctional medications that target multiple disease processes. Fisetin, a naturally occurring flavonol found in strawberries, apples, and onions, has extraordinary potential as a neuroprotective agent due to its anti-inflammatory, anti-apoptotic, and antioxidant properties. Fisetin can cross the blood–brain barrier where it exerts neurotrophic effects through its ability to increase brain-derived neurotrophic factor (BDNF) and stimulate multiple signaling pathways including ERK/MAPK and CREB which collectively increases synaptic plasticity and long-term potentiation. Fisetin also protects mitochondrial function by reducing oxidative stress, maintaining membrane potential and inhibiting apoptosis through cytochrome c. Fisetin inhibits tau hyperphosphorylation, amyloid-beta (Aβ) accumulation, and neuroinflammation while suppressing glial activation and pro-inflammatory cytokine release. In addition, fisetin has senolytic activity by activating the clearance of senescent cells and restoring a healthier neuronal context. Collectively, these multitarget activities support further clinical research of fisetin's therapeutic promise for both Alzheimer's disease prevention and treatment