摘要
大量证据表明慢性脑灌注不足是阿尔茨海默病的相关发病机理。中年肥胖与老年认知丧失及AD发生的风险相关。脑血流量与内皮细胞释放的NO合成作用增加相关,肥胖可以减少脑血流量,也可以增强氧化应激反应。升高的血浆不对称性二甲基精氨酸水平通过抑制NO合成酶活性减少NO产生,从而导致AD病人的脑灌注不足及认知和神经退行性病变。脂联素通过eNOS依赖机制对大脑产生保护作用。肥胖诱导的内皮功能紊乱和脑灌注不足可以增强β淀粉样蛋白的产生,转而损害内皮功能。这种恶性循环,促进了病变而导致AD的形成。通过增强NO对脑血流量的调节作用打破这种循环,预期促进预防AD 发病源。本文对预防或治疗措施的研究进展进行了总结,包括体育运动、营养充足的饮食摄入、药物治疗如乙酰胆碱抑制剂和抗氧化剂、及肥胖外科手术,他们对保护和延缓认知丧失及神经退化的过程很有效。
关键词: 阿尔茨海默病,β淀粉样,脑血流量,内皮功能,一氧化氮,肥胖
Current Alzheimer Research
Title:Obesity-Induced Cerebral Hypoperfusion Derived from Endothelial Dysfunction: One of the Risk Factors for Alzheimer's Disease
Volume: 11 Issue: 8
Author(s): Noboru Toda, Kazuhide Ayajiki and Tomio Okamura
Affiliation:
关键词: 阿尔茨海默病,β淀粉样,脑血流量,内皮功能,一氧化氮,肥胖
摘要: Increasing evidence supports the idea that chronic hypoperfusion in the brain is responsible for the pathogenesis underling Alzheimer’s disease (AD). Obesity at midlife is associated with the risk of cognitive loss and AD at later life. Obesity decreases cerebral blood flow that is associated with decreased synthesis and actions of nitric oxide (NO) derived from the endothelium and also increases the production of oxidative stress. Increased plasma levels of asymmetric dimethylarginine decreases the production of NO by inhibiting NO synthase activity, leading to cerebral hypoperfusion and cognitive and neurodegenerative changes in AD. Adiponectin has a cerebroprotective action through an eNOSdependent mechanism. Obesity-induced endothelial dysfunction and cerebral hypoperfusion enhance the production of β-amyloid that in turn impairs endothelial function; this vicious cycle promotes the pathogenic changes leading to AD. Interrupting this cycle by enhancement of NO-mediated cerebral blood flow is expected to promote prophylaxis against AD pathogenesis. This review summarizes recent advances in prophylactic or therapeutic measures, including physical exercise, nutritionally adequate dietary intake, pharmacological treatments such as acetylcholinesterase inhibitors and antioxidants, and bariatric surgery that are efficient in protecting and retarding the progress of cognitive failure and neurodegeneration.
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Cite this article as:
Noboru Toda, Kazuhide Ayajiki and Okamura Tomio, Obesity-Induced Cerebral Hypoperfusion Derived from Endothelial Dysfunction: One of the Risk Factors for Alzheimer's Disease, Current Alzheimer Research 2014; 11 (8) . https://dx.doi.org/10.2174/156720501108140910120456
DOI https://dx.doi.org/10.2174/156720501108140910120456 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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