Decoding BDNF in neurodevelopmental, neurodegenerative, and neurological disorders: mechanisms and therapeutic perspectives.

Brain-Derived Neurotrophic Factor (BDNF) is an essential neurotrophin involved in neuronal survival, synaptic plasticity, and neurogenesis, critical for normal brain function as well as the pathology of neurological and psychiatric disorders. It primarily functions by activating TrkB receptors, which subsequently modulate intracellular signalling pathways such as PI3K-Akt, Ras-MAPK, and PLC-γ1. The expression of BDNF is precisely controlled by genetic, epigenetic, and transcriptional mechanisms, with environmental and activity-dependent factors providing further modulation. However, it is worth noting that BDNF dysregulation has been linked to major diseases such as depression, schizophrenia, autism spectrum disorder, epilepsy, Alzheimer’s disease (AD), and Parkinson’s disease (PD), and depression, with growing evidence supporting its use as a biomarker for disease monitoring and treatment. This review provides a comprehensive overview of BDNF synthesis, regulation, and signalling mechanisms, highlighting its context-dependent roles in both health and disease. It also examines the role of BDNF in cerebellar development, specifically its effects on granule cells, Purkinje cells, and interneurons govern neuronal survival, migration, and synaptic refinement, and its disruption may predispose to neuropsychiatric vulnerability. While BDNF modulation correlates with clinical outcomes, it remains unclear whether BDNF upregulation directly contributes to therapeutic efficacy or is merely an associated response. BDNF shows promise as a diagnostic biomarker and therapeutic target, merging mechanistic and clinical insights, but requires further research for full potential in precision medicine.