Neuroprotective Potential of Quercetin in Alzheimer's Disease: Targeting Oxidative Stress, Mitochondrial Dysfunction, and Amyloid-β Aggregation

Mohd Adnan¹Arif Jamal Siddiqui¹Fevzi Bardakci¹Dr. Malvi Surti²Riadh Badraoui¹Mitesh Patel^2*

• ¹University of Hail, Ha'il, Hail, Saudi Arabia
• ²Parul University, Waghodia, India

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) peptide accumulation, oxidative stress, mitochondrial dysfunction and cholinergic deficits, leading to neuronal damage. This study evaluates the neuroprotective potential of quercetin, a natural flavonoid, against Aβ-induced toxicity in human neuroblastoma SH-SY5Y cells. The obtained results demonstrate that quercetin significantly enhances cell viability by reducing oxidative stress, as evidenced by a decrease in reactive oxygen species (ROS) levels. Quercetin also stabilizes mitochondrial membrane potential (ΔΨm), preventing mitochondrial dysfunction, which is a key factor in Aβ-induced neurotoxicity. Additionally, quercetin inhibits acetylcholinesterase (AChE), thereby preserving cholinergic function, which is crucial for memory and cognition. Furthermore, quercetin prevents Aβ aggregation, reducing the formation of toxic amyloid fibrils that contribute to neuronal toxicity. By targeting multiple pathological mechanisms, including oxidative stress, mitochondrial dysfunction, AChE activity and Aβ aggregation, quercetin exhibits strong neuroprotective properties. These results suggest that quercetin could be a promising natural therapeutic agent for AD and other neurodegenerative disorders. However, further in-vivo studies and clinical trials are needed to validate its efficacy and explore its potential applications in neurodegenerative disease management.