期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 32, 期 3, 页码 569-578出版社
IOS PRESS
DOI: 10.3233/JAD-2012-120670
关键词
Acetylcholinesterase inhibitor; Alzheimer's disease; cerebral blood flow; endothelial dysfunction; nitric oxide; parasympathetic nitrergic nerve
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [23390055]
- Grants-in-Aid for Scientific Research [23390055] Funding Source: KAKEN
Cerebral hypoperfusion due to impaired bioavailability of nitric oxide (NO) synthesized by endothelial nitric oxide synthase and neuronal nitric oxide synthase leads to cognitive decline and neurodegeneration in Alzheimer's disease (AD). Risk factors for endothelial dysfunction, such as inadequate lifestyle, cardiovascular/metabolic diseases, and aging, evokes cerebral hypoperfusion, impaired autoregulation, and increased production of amyloid-beta peptides (A beta) in association with vasculogenic memory loss and dementia. Decrease in parasympathetic nitrergic nerve activity also plays a role in cerebral hypoperfusion. A beta is a functional obstacle to NO-mediated vasodilatation; therefore, it decreases cerebral blood flow. Generation of reactive oxygen species by A beta is a major action in promoting NO degradation. Effective strategies for the prophylaxis or treatment of AD includes acetylcholinesterase inhibitors, drugs acting on the NO-cyclic GMP signaling pathway, antioxidants, peroxisome proliferator-activated receptor gamma-agonists, and hydroxymethylglutaryl-CoA reductase inhibitors. Here our hypothesis about the mechanisms underlying the actions of acetylcholinesterase inhibitors in relation to NO-mediated cerebral blood flow is presented. Future detailed analyses of the relationship between cerebral blood flow regulation by constitutive NO and cognitive decline/neurodegeneration will provide clues for developing novel prophylactic measures and therapeutic means to alleviate AD.
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