The contact activation system and vascular factors as alternative targets for Alzheimer's disease therapy.
The contact activation system and vascular factors as alternative targets for Alzheimer's disease therapy.
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DOI：
10.1002/rth2.12504
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发表时间：
2021-05
影响因子：
4.6
通讯作者：
Norris EH
中科院分区：
文献类型：
--
作者：
Singh PK;Badimon A;Chen ZL;Strickland S;Norris EH
阿尔茨海默病（AD）是最常见的神经退行性疾病，影响着全世界数百万人。细胞外β -淀粉样蛋白（Aβ）斑块和神经原纤维tau蛋白缠结是阿尔茨海默病病理的典型标志，因此是阿尔茨海默病治疗的主要目标。然而，通过减少Aβ产生、中和毒性Aβ聚集或抑制tau聚集来减缓或阻止AD进展和痴呆的方法在临床试验中大多不成功。在AD病理中，血管成分失调和炎症的作用是显而易见的。血管变化在AD进展的早期就可以检测到，因此血管缺陷治疗与抗a β/tau治疗可能是一种成功的联合治疗策略。在这里，我们解释血管功能障碍如何在AD发病机制中促进血栓形成、炎症和神经退行性变。这篇综述提供了证据，表明处理AD患者的血管功能障碍可能是一种很有前途的治疗策略。
Alzheimer's disease (AD) is the most common neurodegenerative disease, affecting millions of people worldwide. Extracellular beta‐amyloid (Aβ) plaques and neurofibrillary tau tangles are classical hallmarks of AD pathology and thus are the prime targets for AD therapeutics. However, approaches to slow or stop AD progression and dementia by reducing Aβ production, neutralizing toxic Aβ aggregates, or inhibiting tau aggregation have been largely unsuccessful in clinical trials. The contribution of dysregulated vascular components and inflammation is evident in AD pathology. Vascular changes are detectable early in AD progression, so treatment of vascular defects along with anti‐Aβ/tau therapy could be a successful combination therapeutic strategy for this disease. Here, we explain how vascular dysfunction mechanistically contributes to thrombosis as well as inflammation and neurodegeneration in AD pathogenesis. This review provides evidence that addressing vascular dysfunction in people with AD could be a promising therapeutic strategy.
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影响因子：
--
作者：
Craft, Suzanne
通讯作者：
Craft, Suzanne
影响因子：
12.7
作者：
Arbel-Ornath M;Hudry E;Eikermann-Haerter K;Hou S;Gregory JL;Zhao L;Betensky RA;Frosch MP;Greenberg SM;Bacskai BJ
通讯作者：
Bacskai BJ
影响因子：
16.2
作者：
Cortes-Canteli, Marta;Paul, Justin;Norris, Erin H.;Bronstein, Robert;Ahn, Hyung Jin;Zamolodchikov, Daria;Bhuvanendran, Shivaprasad;Fenz, Katherine M.;Strickland, Sidney
通讯作者：
Strickland, Sidney
影响因子：
20.3
作者：
Chen, Zu-Lin;Revenko, Alexey S.;Strickland, Sidney
通讯作者：
Strickland, Sidney
DOI：
10.1073/pnas.1914831116
发表时间：
2019-11-12
影响因子：
11.1
作者：
Chen, Zu-Lin;Singh, Pradeep;Norris, Erin H.
通讯作者：
Norris, Erin H.