中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 198-206.doi: 10.4103/1673-5374.226379

• 综述:退行性病与再生 • 上一篇    下一篇

他汀类药物对β淀粉样蛋白诱导的神经毒性的神经保护作用

  

  • 收稿日期:2018-01-16 出版日期:2018-02-15 发布日期:2018-02-15

Neuroprotective effects of statins against amyloid β-induced neurotoxicity

Hsin-Hua Li1, Chih-Li Lin1, 3, Chien-Ning Huang1, 2   

  1. 1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, China
    2 Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, China
    3 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, China
  • Received:2018-01-16 Online:2018-02-15 Published:2018-02-15
  • Contact: Chien-Ning Huang, M.D.,Ph.D., cshy049@gmail.com.
  • Supported by:

    This work was supported by the grant from the Ministry of Science and Technology of Taiwan, China (MOST 105-2314-B-013-MY3 and MOST 106-2320-B-040-021-MY3).

摘要:

orcid:0000-0003-4668-7998(Chien-Ning Huang)

Abstract:

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.

Key words: statins, neuroprotective effects, amyloid β-induced neurotoxicity, insulin signaling, AMP-activated protein kinase