Targeting Autophagy with Bioactive Compounds: Therapeutic Potential in Neurodegenerative Disorders

Neurodegenerative disorders (NDs), including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are characterized by the accumulation of misfolded proteins and impaired cellular clearance mechanisms. Autophagy, a critical lysosomedependent degradative pathway, plays a vital role in maintaining proteostasis and neuronal health. Dysregulation of autophagy has been implicated in the pathogenesis of multiple NDs, making it a promising therapeutic target. This review comprehensively examines the molecular mechanisms of autophagy and its dysfunction across major NDs. Furthermore, it highlights the potential of bioactive compounds such as flavonoids, alkaloids, polyphenols, and terpenoids to modulate autophagic flux, thereby promoting the clearance of toxic protein aggregates like amyloid-β, tau, and α- synuclein. Emerging strategies, including nanotechnology-based delivery systems, are also discussed for enhancing the bioavailability and efficacy of these compounds. The evidence suggests that pharmacological or natural induction of autophagy may alleviate neurodegenerative pathology, though context- and stage-specific modulation is essential. This work underscores the therapeutic promise of autophagy-enhancing bioactives and calls for further research into their clinical applications.