Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer's Disease

Ahmed Morsy, Paul C. Trippier

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
Pages (from-to)4252-4264
Number of pages13
JournalJournal of Medicinal Chemistry
Volume62
Issue number9
DOIs
StatePublished - May 9 2019

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Alcohol Dehydrogenase
Amyloid
Alzheimer Disease
Estradiol
Peroxiredoxins
Estrone
Mitochondrial Proteins
Dementia
Reactive Oxygen Species
Proteins
Pharmacology
Apoptosis
Neurons

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer's Disease. / Morsy, Ahmed; Trippier, Paul C.

In: Journal of Medicinal Chemistry, Vol. 62, No. 9, 09.05.2019, p. 4252-4264.

Research output: Contribution to journalReview article

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