Quercetin as a Multi-Target Therapeutic Candidate in Amyotrophic Lateral Sclerosis: From Molecular Mechanisms to Nano-Delivery and Senolytic Strategies

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that destroys motor neurons, leading to progressive paralysis and death usually within 2–5 years. Current drugs such as riluzole and edaravone offer only modest benefit, making new treatments urgently needed. Quercetin, a natural plant-derived flavonoid found in everyday foods, acts on multiple disease mechanisms at once — it fights oxidative stress, reduces neuroinflammation, prevents toxic protein clumping, protects mitochondria, and can even selectively destroy harmful senescent cells (“zombie” cells) that drive inflammation in the spinal cord. However, quercetin poorly dissolves in water, is rapidly broken down in the gut and liver, and barely crosses the blood-brain barrier (BBB). This review explains what makes quercetin scientifically promising for ALS, how nano-engineered drug carriers such as PLGA nanoparticles, lipid carriers, and exosomes can overcome these delivery problems, and how combining quercetin with the senolytic drug dasatinib might slow ALS progression. Key research gaps and steps needed before quercetin-based therapies can enter clinical trials for ALS patients are also discussed.