Akademik Veri Yönetim Sistemi
12th INTERNATIONAL EUROPEAN CONFERENCE ON INTERDISCIPLINARY SCIENTIFIC RESEARCH , Rome, İtalya, 11 - 13 Temmuz 2025, ss.751-757, (Tam Metin Bildiri)
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) plaques and hyperphosphorylated tau aggregates. Autophagy, a highly conserved intracellular degradation pathway, facilitates the clearance of cytoplasmic components such as misfolded proteins and damaged organelles via lysosomal digestion. Mounting evidence indicates that dysregulation of autophagy contributes significantly to AD pathogenesis from the early stages, particularly through impaired autophagosome-lysosome fusion, accumulation of autophagic vacuoles, and downregulation of key autophagy-related proteins such as Beclin-1. In this context, pharmacological enhancement of autophagy has emerged as a promising therapeutic strategy. A growing number of clinically approved agents—originally developed for other indications—have been identified as autophagy inducers and proposed for drug repositioning in AD. Notably, mTORC1 inhibitors (e.g., rapamycin), AMPK activators (e.g., trehalose), and compounds modulating inositol metabolism (e.g., lithium, valproic acid, carbamazepine) have been shown to enhance autophagic flux, reduce Aβ and tau burden, and improve cognitive function in preclinical models. Drug repositioning offers significant advantages in terms of development time, safety profiles, and cost-effectiveness, making it a highly attractive strategy for complex disorders such as AD. This review highlights the molecular rationale for targeting impaired autophagy in AD and evaluates the therapeutic relevance of repositioned drugs, offering a translational perspective for novel interventions in neurodegenerative disease.