Genetic variations in BDNF: therapeutic potential and influence on neuroregeneration in neurodegenerative diseases

Brain-derived neurotrophic factor (BDNF) is essential for neuronal survival and plasticity. An in silico analysis was performed on missense variants of BDNF retrieved from dbSNP and UniProt, filtered by allele frequency and evaluated through a consensus of 13 predictive tools (PredictSNP1.0, iStable, and DynaMut2) to estimate their effects on protein stability and dynamics. Among the 25.241 reported variants, eight substitutions were prioritized as potentially deleterious, five of which were examined in greater detail due to their predicted impact on protein stability. High-confidence variants were structurally inspected using the AlphaFold model (AF-P23560-F1) to ensure reproducibility. These findings provide a set of candidate variants that may alter BDNF structural properties; however, experimental validation is required and will serve as a foundation for future investigations into their functional relevance and therapeutic implications in neurodegenerative diseases.