Current advances in PDGF isoform specificity and variable functions in aging-associated neurological disorders

Among the signaling molecules that influence the health and pathology of central nervous system (CNS), Platelet-derived growth factor (PDGF) has emerged as a pivotal regulator of neurogenesis, neuroinflammation, and neuronal survival. However, the isoform-specific signaling of PDGF in aging-related neurological disorders remains under-characterized, and the interplay between PDGF and cellular senescence in CNS is inadequately understood. Additionally, the dual role of PDGFs signaling remains underexplored, especially in aging-related neurological disorders. This review aims to address these gaps by analyzing the roles of five PDGF isoforms in CNS functions, PDGFs downstream signaling in the nervous system, PDGF's modulation of neural components, and its role in aging-related diseases including Stroke, Alzheimer's Disease (AD), Parkinson's Disease (PD), and Glioblastoma (GBM). In this review, we highlight the effects of PDGF isoforms in the CNS vary with experimental conditions, dosage, cellular microenvironment and aging status. This review provides a comparative analysis of PDGF isoform-specific functions, emphasizing age-dependent signaling shifts and potential therapeutic implications.