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ID: ALA4396863
Journal: J Med Chem
Title: Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer's Disease.
Authors: Morsy A, Trippier PC.
Abstract: 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.
CiteXplore: 30444369