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血管性痴呆和阿尔茨海默病中的髓样细胞:可能的治疗靶点?

Myeloid cells in vascular dementia and Alzheimer's disease: Possible therapeutic targets?

机构信息

Cardiovascular Risk Factor and Brain Function Programme, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.

Unidad de Investigación Neurovascular, Departamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid (UCM), Madrid, Spain.

出版信息

Br J Pharmacol. 2024 Mar;181(6):777-798. doi: 10.1111/bph.16159. Epub 2023 Jul 7.

Abstract

Growing evidence supports the suggestion that the peripheral immune system plays a role in different pathologies associated with cognitive impairment, such as vascular dementia (VD) or Alzheimer's disease (AD). The aim of this review is to summarize, within the peripheral immune system, the implications of different types of myeloid cells in AD and VD, with a special focus on post-stroke cognitive impairment and dementia (PSCID). We will review the contributions of the myeloid lineage, from peripheral cells (neutrophils, platelets, monocytes and monocyte-derived macrophages) to central nervous system (CNS)-associated cells (perivascular macrophages and microglia). Finally, we will evaluate different potential strategies for pharmacological modulation of pathological processes mediated by myeloid cell subsets, with an emphasis on neutrophils, their interaction with platelets and the process of immunothrombosis that triggers neutrophil-dependent capillary stall and hypoperfusion, as possible effector mechanisms that may pave the way to novel therapeutic avenues to stop dementia, the epidemic of our time. LINKED ARTICLES: This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

摘要

越来越多的证据表明,外周免疫系统在与认知障碍相关的不同病理中发挥作用,如血管性痴呆 (VD) 或阿尔茨海默病 (AD)。本综述的目的是总结外周免疫系统中不同类型的髓样细胞在 AD 和 VD 中的作用,特别关注中风后认知障碍和痴呆 (PSCID)。我们将回顾骨髓谱系的贡献,从外周细胞(中性粒细胞、血小板、单核细胞和单核细胞衍生的巨噬细胞)到中枢神经系统 (CNS) 相关细胞(血管周巨噬细胞和小胶质细胞)。最后,我们将评估不同的潜在策略,以调节髓样细胞亚群介导的病理过程,重点是中性粒细胞、它们与血小板的相互作用以及引发中性粒细胞依赖性毛细血管停滞和灌注不足的免疫血栓形成过程,作为可能开辟新的治疗途径以阻止痴呆的有效机制,这是我们这个时代的流行病。相关文章:本文是从阿尔茨海默病到血管性痴呆:不同的认知衰退之路专题的一部分。要查看本节中的其他文章,请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc.

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