Research Department, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS ISMETT), Palermo, Italy.
Neurology Service, Department of Diagnostic and Therapeutic Services, Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS ISMETT), Palermo, Italy.
Mech Ageing Dev. 2020 Oct;191:111332. doi: 10.1016/j.mad.2020.111332. Epub 2020 Aug 15.
Age is the pivotal risk factor for different common medical conditions such as cardiovascular diseases, cancer and dementia. Among age-related disorders, cardiovascular and cerebrovascular diseases, represent the leading causes of premature mortality strictly related to vascular ageing, a pathological condition characterized by endothelial dysfunction, atherosclerosis, hypertension, heart disease and stroke. These features negatively impact on the brain, owing to altered cerebral blood flow, neurovascular coupling and impaired endothelial permeability leading to cerebrovascular diseases (CVDs) as Vascular Dementia (VD) and Parkinsonism (VP). It is an increasing opinion that neurodegenerative disorders and cerebrovascular diseases are associated from a pathogenetic point of view, and in this review, we discuss how cerebrovascular dysfunctions, due to epigenetic alterations, are linked with neuronal degeneration/dysfunction that lead to cognitive impairment. The relation between neurodegenerative and cerebrovascular diseases are reviewed with a focus on role of ncRNAs in age-related vascular diseases impairing the endothelium in the blood-brain barrier with consequent dysfunction of cerebral blood flow. In this review we dissert about different regulatory mechanisms of gene expression implemented by ncRNAs in the pathogenesis of age-related neurovascular impairment, aiming to highlight the potential use of ncRNAs as biomarkers for diagnostic/prognostic purposes as well as novel therapeutic targets.
年龄是心血管疾病、癌症和痴呆等多种常见医学病症的关键风险因素。在与年龄相关的疾病中,心血管和脑血管疾病是与血管老化密切相关的过早死亡的主要原因,血管老化是一种以内皮功能障碍、动脉粥样硬化、高血压、心脏病和中风为特征的病理状态。这些特征对大脑产生负面影响,因为改变了脑血流、神经血管耦联和内皮通透性,导致血管性痴呆(VD)和帕金森病(VP)等脑血管疾病(CVDs)。越来越多的观点认为,神经退行性疾病和脑血管疾病从发病机制上是相关的,在这篇综述中,我们讨论了由于表观遗传改变,脑血管功能障碍如何与导致认知障碍的神经元变性/功能障碍相关。本文综述了神经退行性疾病和脑血管疾病之间的关系,重点讨论了 ncRNAs 在与年龄相关的血管疾病中对内皮功能的损害,导致血脑屏障的脑血流功能障碍。在这篇综述中,我们论述了 ncRNAs 在与年龄相关的神经血管损伤发病机制中实施的不同基因表达调控机制,旨在强调 ncRNAs 作为诊断/预后目的的生物标志物以及新型治疗靶点的潜在用途。