Akademik Veri Yönetim Sistemi
MOLECULAR NEUROBIOLOGY, cilt.63, sa.1, 2026 (SCI-Expanded, Scopus)
Alzheimer's disease (AD) is a complex neurodegenerative condition involving beta-amyloid (A beta) deposition, tau abnormalities, neuroinflammation, neuronal degeneration, and progressive impairment of cognitive functions. Despite extensive research, effective disease-modifying therapies remain limited, highlighting the need for translationally relevant models and repurposable therapeutic candidates. Dexmedetomidine (DEX), an alpha 2-adrenergic receptor agonist with known neuroprotective properties, was investigated in an adult zebrafish model of AD established through cerebroventricular administration of A beta 42. DEX treatment significantly reduced A beta accumulation and was associated with reduced amyloidogenic gene expression, indicating transcriptional changes in amyloidogenic pathway-related genes. DEX attenuated neuroinflammation by reducing glial activation, lowering pro-inflammatory cytokine gene expression, and increasing expression of the anti-inflammatory gene il10. Immunofluorescence assessment further demonstrated reduced astrogliosis and preserved neuronal marker integrity, as indicated by increased HuC/D levels. Interestingly, DEX attenuated A beta-induced proliferative responses, characterized by decreased PCNA expression, while enhancing cleaved caspase-3 levels, suggesting changes in proliferation and apoptotic signaling under A beta stress conditions. Behavioral assessments further demonstrated that DEX alleviated A beta 42-induced anxiety- and aggression-like behaviors, improving behavioral phenotypes in this model. Overall, these findings underscore the multi-level effects of DEX in modulating AD-related pathological features. As a clinically available agent, DEX represents a promising candidate for repurposing in neurodegenerative disease contexts. Further preclinical studies in mammalian models are warranted to validate its translational relevance and therapeutic potential.