Department of Pharmacology and Toxicology, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia.
Pharmacoepidemiology and Social Pharmacy Unit, School of Pharmacy, College of Health Sciences, Mekelle University, Mekelle, Ethiopia.
Biomed Res Int. 2020 Feb 18;2020:9895121. doi: 10.1155/2020/9895121. eCollection 2020.
Alzheimer's disease is a multifactorial neurodegenerative disease characterized by progressive cognitive dysfunction. It is the most common form of dementia. The pathologic hallmarks of the disease include extracellular amyloid plaque, intracellular neurofibrillary tangles, and oxidative stress, to mention some of them. Despite remarkable progress in the understanding of the pathogenesis of the disease, drugs for cure or disease-modifying therapy remain somewhere in the distance. From recent time, the signaling molecule AMPK is gaining enormous attention in the AD drug research. AMPK is a master regulator of cellular energy metabolism, and recent pieces of evidence show that perturbation of its function is highly ascribed in the pathology of AD. Several drugs are known to activate AMPK, but their effect in AD remains to be controversial. In this review, the current shreds of evidence on the effect of AMPK activators in A accumulation, tau aggregation, and oxidative stress are addressed. Positive and negative effects are reported with regard to A and tauopathy but only positive in oxidative stress. We also tried to dissect the molecular interplays where the bewildering effects arise from.
阿尔茨海默病是一种多因素神经退行性疾病，其特征是进行性认知功能障碍。它是最常见的痴呆症形式。该疾病的病理标志物包括细胞外淀粉样斑块、细胞内神经原纤维缠结和氧化应激等。尽管人们在理解该疾病的发病机制方面取得了显著进展，但治愈或疾病修饰疗法的药物仍遥遥无期。最近，信号分子 AMPK 在 AD 药物研究中受到了极大关注。AMPK 是细胞能量代谢的主要调节剂，最近的证据表明，其功能的紊乱在 AD 的病理中高度归因。有几种已知的药物可以激活 AMPK，但它们在 AD 中的作用仍存在争议。在这篇综述中，我们讨论了 AMPK 激活剂在 A 积聚、tau 聚集和氧化应激方面的作用的现有证据。关于 A 和 tau 病有正面和负面的影响，但只有在氧化应激方面是正面的。我们还试图剖析分子相互作用，从中产生令人困惑的影响。
