Insights Into the Role of Platelet Factor 4 in Neurodegenerative Diseases

As population aging accelerates worldwide, the prevalence and burden of neurodegenerative diseases (NDs) continue to rise, underscoring the urgent need to identify key molecular mechanisms driving disease progression and novel therapeutic targets. Chronic neuroinflammation is a hallmark of multiple NDs, including Alzheimer's disease and Parkinson's disease. Platelet factor 4 (PF4) is a chemokine primarily released by activated platelets and has traditionally been investigated for its roles in hemostasis, thrombosis, and peripheral inflammation.

Growing evidence has implicated PF4 in the pathogenesis of NDs. Altered PF4 expression has been observed across multiple NDs. As a central player at the intersection of the nervous, immune, and vascular systems, PF4 modulates inflammation, vascular homeostasis, and neuronal survival, all of which are critical in the pathogenesis of NDs. Dissecting the cell-type specific and temporally dynamic roles of PF4 across diverse disease contexts is essential for elucidating its contribution to neurodegenerative processes and disease progression.

This review highlights PF4 as a potential mechanistic mediator in NDs and discusses its promise as both a biomarker and a therapeutic target. Further elucidation of PF4 signaling pathways may provide new insights into disease mechanisms and uncover novel opportunities for targeted interventions in NDs.