Platelets: A new therapeutic target for neurological diseases

IF 12.4 1区医学 Q1 CELL BIOLOGY

Ageing Research Reviews Pub Date : 2025-08-15 DOI:10.1016/j.arr.2025.102874

Xin-Xin Wei , Xiao-Qing Tang

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Abstract

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.

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血小板：神经系统疾病的新治疗靶点

除了在止血和凝血中的经典作用外，越来越多的证据表明血小板在神经系统中具有多方面的调节作用。研究表明，血小板衍生因子通过神经化学途径促进血脑屏障（BBB）成熟和血管生成。同时，富血小板血浆（PRP）通过减轻β淀粉样蛋白（Aβ）的神经毒性和激活PI3k/Akt信号通路来促进神经再生。血小板还通过NMDA受体依赖机制调节突触可塑性，并调节神经递质的合成。病理上，血小板是神经退行性变的关键因素。它们通过释放Aβ和促进tau过度磷酸化来加剧阿尔茨海默病（AD）的病理，通过p2y12介导的血小板-白细胞聚集和血清素失调引发偏头痛，并通过cd40l依赖性血脑屏障破坏放大多发性硬化症（MS）的神经炎症。相反，使用PAFR拮抗剂（银杏内酯B）、P2Y12抑制剂（氯吡格雷）或环氧化酶调节剂（阿司匹林）抑制血小板活化可以减轻神经炎症，减少病理性蛋白积累，促进功能恢复。本文综述了血小板在神经系统生理学和神经病理学中的机制作用，并提出了新的血小板靶向预防和治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ageing Research Reviews 医学-老年医学

CiteScore

19.80

自引率

2.30%

发文量

216

审稿时长

55 days

期刊介绍： With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.