Title : Translational insights into molecular mechanisms and neurodegeneration: Bridging experimental models and clinical realities
Abstract:
Neurodegenerative disorders, including Alzheimer's and Parkinson's disease, remain a critical global health crisis characterized by progressive cellular dysfunction, protein aggregation, and neuronal loss. Despite extensive preclinical research, translating laboratory breakthroughs into effective clinical therapies remains a major challenge. This study aims to systematically evaluate the molecular cascades driving neurodegeneration and examine the translational gap between experimental models and clinical trial outcomes.
A comprehensive literature review methodology was utilized, analyzing peer-reviewed articles, clinical trial records, and open-science datasets focused on molecular neurobiology. Research from the past decade was rigorously evaluated to assess mechanistic intersections, biomarker discovery, and cross-species pathological comparisons.
The review identifies significant divergence between preclinical animal models and human pathology, largely driven by oversimplified designs, underrepresented genetic diversity, and inconsistent endpoints. Critical mechanisms-such as mitochondrial impairment, neuroinflammation, proteostatic stress, and synaptic vulnerability-exhibit high variability when translated from controlled settings to diverse clinical populations.
These discrepancies highlight fundamental limitations in current preclinical validation pipelines. Overcoming this divide necessitates adopting multi-omics data integration, human-derived cellular models, and decentralized open-science repositories to improve patient stratification and target validation.
Refining experimental frameworks and aligning preclinical metrics with clinical phenotypes are vital for accelerating the development of efficacious, disease-modifying therapies for neurodegenerative diseases.
