化学
神经毒性
阿尔茨海默病
淀粉样蛋白(真菌学)
活性氧
药理学
醇脱氢酶
淀粉样疾病
痴呆
疾病
生物化学
细胞生物学
毒性
淀粉样β
酶
内科学
医学
生物
无机化学
有机化学
淀粉样纤维
作者
Ahmed Morsy,Paul C. Trippier
标识
DOI:10.1021/acs.jmedchem.8b01530
摘要
Alzheimer’s disease (AD) is the most common dementia. No cure exists, and current treatment only manages early symptoms. Mitochondrial dysfunction is a hallmark of amyloid-β (Aβ) neurotoxicity, the pathogenic protein implicated in AD. This is due in part to the interaction between Aβ and amyloid-binding alcohol dehydrogenase (ABAD). This mitochondrial protein is a vital energy regulator that, following Aβ binding, activates signaling cascades that lead to neuronal death. One of the most significant roles of ABAD is to maintain the balance of estradiol/estrone in neurons. However, the Aβ–ABAD interaction disrupts this balance and leads to a reduction in levels of estradiol, thus leading to an increase in reactive oxygen species levels and to apoptosis. Two additional proteins, peroxiredoxin-2 and endophilin-1, are implicated in Aβ–ABAD complex-mediated toxicity. Targeting the Aβ–ABAD interaction has emerged as a novel therapeutic strategy for AD. Herein, we review the chemistry and pharmacology of reported ABAD inhibitors.
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