Platelets: A new therapeutic target for neurological diseases

Beyond their classical roles in hemostasis and coagulation, accumulating evidence highlights platelets as multifaceted regulators within the nervous system. Research has revealed that platelet-derived factors promote blood-brain barrier (BBB) maturation and angiogenesis via neurochemical pathways. At the same time, platelet-rich plasma (PRP) facilitates neural regeneration by mitigating the neurotoxicity of amyloid-beta (Aβ) and activating the PI3k/Akt signaling pathway. Platelets also modulate synaptic plasticity through NMDA receptor-dependent mechanisms and regulate the synthesis of neurotransmitters. Pathologically, platelets emerge as key contributors to neurodegeneration. They exacerbate Alzheimer's disease (AD) pathology by releasing Aβ and promoting tau hyperphosphorylation, trigger migraines via P2Y12-mediated platelet-leukocyte aggregates and serotonin dysregulation, and amplify neuroinflammation in multiple sclerosis (MS) through CD40L-dependent BBB disruption. Conversely, inhibiting platelet activation using PAFR antagonists (Ginkgolide B), P2Y12 inhibitors (Clopidogrel), or cyclooxygenase modulators (Aspirin) can alleviate neuroinflammation, reduce pathological protein accumulation, and promote functional recovery. This review summarizes the mechanistic roles of platelets in both nervous system physiology and neuropathology, proposing novel platelet-targeted preventive and therapeutic strategies.