Current Understanding of Platelet-Activating Factor Signaling in Central Nervous System Diseases

Platelet-activating factor (PAF) is a bioactive lipid mediator which serves as a reciprocal messenger between the immune and nervous systems. PAF, a pluripotent inflammatory mediator, is extensively expressed in many cells and tissues and has either beneficial or detrimental effects on the progress of inflammation-related neuropathology. Its wide distribution and various biological functions initiate a cascade of physiological or pathophysiological responses during development or diseases. Current evidence indicates that excess PAF accumulation in CNS diseases exacerbates the inflammatory response and pathological consequences, while application of PAF inhibitors or PAFR antagonists by blocking this signaling pathway significantly reduces inflammation, protects cells, and improves the recovery of neural functions. In this review, we integrate the current findings of PAF signaling in CNS diseases and elucidate topics less appreciated but important on the role of PAF signaling in neurological diseases. We propose that the precise use of PAF inhibitors or PAFR antagonists that target the specific neural cells during the appropriate temporal window may constitute a potential therapy for CNS diseases.