The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease.
The Role of Chronic Inflammatory Bone and Joint Disorders in the Pathogenesis and Progression of Alzheimer's Disease.
复制标题
DOI：
10.3389/fnagi.2020.583884
复制
发表时间：
2020
影响因子：
4.8
通讯作者：
Hahn MS
中科院分区：
文献类型：
--
作者：
Culibrk RA;Hahn MS
迟发性阿尔茨海默病（LOAD）是一种毁灭性的神经退行性疾病，在全球数千万患者中导致严重的认知衰退。在整个疾病进展过程中，异常分泌酶活性导致大脑细胞外间隙神经毒性β斑块的异常切割和随后的聚集，以及神经元微管周围结构tau蛋白的过度磷酸化和不稳定。这两种病理最终都会刺激与疾病相关的小胶质细胞亚群的繁殖，小胶质细胞是大脑的主要免疫细胞，其特征是优先分泌促炎细胞因子和抑制AD底物摄取能力，这进一步导致神经元变性。几十年来，慢性神经炎症已被确定为阿尔茨海默病的主要病理生理驱动特征之一；然而，尽管许多研究假设了炎症介导的神经退行性变的潜在机制，但其发病机制及其与认知功能障碍的关系仍然不清楚。此外，针对中枢神经系统（CNS）特定病理特征的治疗有限的临床成功表明，需要研究替代的、更全面的方法来改善阿尔茨海默病的结果。越来越多的证据表明，外周免疫活性与血脑屏障通透性、小胶质细胞激活和增殖以及ad相关的认知能力下降之间存在显著的相互作用。在这项工作中，我们回顾了慢性外周炎症条件的一个狭窄但重要的子集，描述了这些病理如何与神经炎症的优势相关，并假设我们可以利用外周免疫过程来设计LOAD的介入性，预防性治疗。然后，我们提供了一个全面的概述，显着的治疗范例，已显示出相当大的优点，以治疗这些疾病。
Late-onset Alzheimer's Disease (LOAD) is a devastating neurodegenerative disorder that causes significant cognitive debilitation in tens of millions of patients worldwide. Throughout disease progression, abnormal secretase activity results in the aberrant cleavage and subsequent aggregation of neurotoxic Aβ plaques in the cerebral extracellular space and hyperphosphorylation and destabilization of structural tau proteins surrounding neuronal microtubules. Both pathologies ultimately incite the propagation of a disease-associated subset of microglia—the principle immune cells of the brain—characterized by preferentially pro-inflammatory cytokine secretion and inhibited AD substrate uptake capacity, which further contribute to neuronal degeneration. For decades, chronic neuroinflammation has been identified as one of the cardinal pathophysiological driving features of AD; however, despite a number of works postulating the underlying mechanisms of inflammation-mediated neurodegeneration, its pathogenesis and relation to the inception of cognitive impairment remain obscure. Moreover, the limited clinical success of treatments targeting specific pathological features in the central nervous system (CNS) illustrates the need to investigate alternative, more holistic approaches for ameliorating AD outcomes. Accumulating evidence suggests significant interplay between peripheral immune activity and blood-brain barrier permeability, microglial activation and proliferation, and AD-related cognitive decline. In this work, we review a narrow but significant subset of chronic peripheral inflammatory conditions, describe how these pathologies are associated with the preponderance of neuroinflammation, and posit that we may exploit peripheral immune processes to design interventional, preventative therapies for LOAD. We then provide a comprehensive overview of notable treatment paradigms that have demonstrated considerable merit toward treating these disorders.
登录
查看更多内容
影响因子：
13.6
作者：
Ankrum J;Karp JM
通讯作者：
Karp JM
DOI：
10.1002/jor.23845
发表时间：
2018-06
期刊：
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
影响因子：
--
作者：
Ball AN;Donahue SW;Wojda SJ;McIlwraith CW;Kawcak CE;Ehrhart N;Goodrich LR
通讯作者：
Goodrich LR
DOI：
10.1002/art.24123
发表时间：
2008-10-15
期刊：
ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH
影响因子：
--
作者：
Aletaha, D.;Landewe, R.;Felson, D.
通讯作者：
Felson, D.
影响因子：
1.6
作者：
Al-Daghri NM;Aziz I;Yakout S;Aljohani NJ;Al-Saleh Y;Amer OE;Sheshah E;Younis GZ;Al-Badr FBM
通讯作者：
Al-Badr FBM
影响因子：
3.8
作者：
Aliabouzar, Mitra;Lee, Se-jun;Sarkar, Kausik
通讯作者：
Sarkar, Kausik