Fibroblast growth factors in Alzheimer's Disease pathogenesis: neuropharmacological implications for neuroprotection, neurogenesis, and therapeutic development.

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by neuroinflammation, synaptic dysfunction, mitochondrial impairment, and cognitive loss. Despite extensive research, disease-modifying therapies remain elusive, underscoring the need to identify novel signalling pathways that could be pharmacologically modified. The diverse family of ligands known as fibroblast growth factors (FGFs) regulates neurogenesis, synaptic plasticity, neuronal survival, and metabolic balance by binding to fibroblast growth factor receptors (FGFRs). Numerous elements of AD pathogenesis, including energy metabolism, tau pathology, amyloid-β-toxicity, and neuroinflammation, are linked to dysregulated FGF-FGFR signalling according to an increasing number of studies. This study critically examines the neuropharmacological roles of FGFs in the central nervous system and their relationship to AD. We discuss how FGF modulates intracellular signalling cascades, including MAPK/ERK, PI3K-AKT, and STAT pathways, and how these changes affect synaptic integrity, glial activation, and neuronal resilience. We also highlight novel relationships among FGFs, metabolic dysfunction in AD, mitochondrial signalling, and gut-brain communication. Finally, we evaluate the therapeutic potential and challenges of targeting FGF signalling, including issues with receptor selectivity, blood-brain barrier penetration, and long-term safety. Collectively, this review positions FGF signalling as a promising yet underexplored neuropharmacological axis for developing disease-modifying strategies in Alzheimer's disease.