期刊
CLINICAL SCIENCE
卷 131, 期 7, 页码 515-531出版社
PORTLAND PRESS LTD
DOI: 10.1042/CS20160825
关键词
-
资金
- Agency for Science, Technology and Research Singapore
- NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust
- King's College London
- British Heart Foundation Immediate Research Fellowship [FS/15/61/31626]
- NIHR Senior Investigator award
- Cambridge Universities Trust NIHR Comprehensive Biomedical Research Centre
- British Heart Foundation [FS/15/61/31626] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10019] Funding Source: researchfish
Cerebral small vessel disease (SVD) is a common cause of lacunar strokes, vascular cognitive impairment (VCI) and vascular dementia. SVD is thought to result in reduced cerebral blood flow, impaired cerebral autoregulation and increased blood-brain barrier (BBB) permeability. However, the molecular mechanisms underlying SVD are incompletely understood. Recent studies in monogenic forms of SVD, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and 'sporadic' SVD have shed light on possible disease mechanisms in SVD. Proteomic and biochemical studies in post-mortem monogenic SVD patients, as well as in animal models of monogenic disease have suggested that disease pathways are shared between different types of monogenic disease, often involving the impairment of extracellular matrix (ECM) function. In addition, genetic studies in 'sporadic' SVD have also shown that the disease is highly heritable, particularly among young-onset stroke patients, and that common variants in monogenic disease genes may contribute to disease processes in some SVD subtypes. Genetic studies in sporadic lacunar stroke patients have also suggested distinct genetic mechanisms between subtypes of SVD. Genome-wide association studies (GWAS) have also shed light on other potential disease mechanisms that may be shared with other diseases involving the white matter, or with pathways implicated in monogenic disease. This review brings together recent data from studies in monogenic SVD and genetic studies in 'sporadic' SVD. It aims to show how these provide new insights into the pathogenesis of SVD, and highlights the possible convergence of disease mechanisms in monogenic and sporadic SVD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据