Neuroprotective effects of statins against amyloid β-induced neurotoxicity.
Neuroprotective effects of statins against amyloid β-induced neurotoxicity.
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DOI：
10.4103/1673-5374.226379
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发表时间：
2018-03
影响因子：
6.1
通讯作者：
Huang CN
中科院分区：
文献类型：
--
作者：
Li HH;Lin CL;Huang CN
越来越多的证据表明，脂质代谢稳态的破坏会影响阿尔茨海默病 (AD) 的发病机制。特别是，据报道，大脑中胆固醇稳态失调会大大增加患 AD 的风险。因此，脂质稳态失调可能通过影响淀粉样前体蛋白（APP）裂解来增加β淀粉样蛋白（Aβ）水平，而APP是AD发病机制中最重要的危险因素。先前的研究表明，Aβ 可以引发神经元胰岛素抵抗，这在 AD 中 Aβ 诱导的神经毒性反应中发挥着重要作用。流行病学研究还表明，他汀类药物的使用与 AD 发病率降低有关。因此，他汀类药物被认为是针对 AD 具有神经保护作用的良好候选者。他汀类药物可能在减少 Aβ 诱导的神经毒性方面发挥有益作用。它们的作用除了降低胆固醇作用之外，还涉及一种假定的机制，可以预防 Aβ 诱导的神经毒性。然而，他汀类药物在 Aβ 诱导的神经毒性中的保护作用的潜在分子机制尚未明确。鉴于他汀类药物的益处可能超出了抑制 3-羟基-3-甲基戊二酰辅酶 A (HMG-CoA) 还原酶的范围，因此这些药物还可能改善大脑功能。因此，他汀类药物可能通过激活神经元细胞中的 AMP 激活蛋白激酶 (AMPK) 对受损的胰岛素信号传导产生有益影响。它们在针对 Aβ 介导的神经毒性方面发挥潜在的治疗作用。
A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD). In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ) levels by affecting amyloid precursor protein (APP) cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuroprotective effects against AD. Statins may play a beneficial role in reducing Aβ-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing Aβ-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase (AMPK) in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.
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影响因子：
5.3
作者：
Corrao, Giovanni;Ibrahim, Buthaina;Mancia, Giuseppe
通讯作者：
Mancia, Giuseppe
阿尔茨海默氏病的GSK3假设。
影响因子：
4.7
作者：
Hooper C;Killick R;Lovestone S
通讯作者：
Lovestone S
影响因子：
82.9
作者：
Geula, C;Wu, CK;Yankner, BA
通讯作者：
Yankner, BA
影响因子：
3.3
作者：
Igbavboa, U.;Sun, G. Y.;Wood, W. G.
通讯作者：
Wood, W. G.
DOI：
10.1186/s13195-017-0237-y
发表时间：
2017-02-17
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Geifman N;Brinton RD;Kennedy RE;Schneider LS;Butte AJ
通讯作者：
Butte AJ