| Title | β-amyloid binding alcohol dehydrogenase as pharmacological target in Alzheimer’s disease | |
| Authors | Ioannis Kiriakidis, Stergios Katsaris and Basile Kokkas
Department of Pharmacology, Medical School, Aristotelian University, Thessaloniki, Greece |
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| Citation | Kiriakidis, I., Katsaris, S., Kokkas, B.: β-amyloid binding alcohol dehydrogenase as pharmacological target in Alzheimer’s disease, Epitheorese Klin. Farmakol. Farmakokinet. 21(2.1): 173-178 (2007) | |
| Publication Date | Accepted for publication (Final version): June 1, 2007 | |
| Full Text Language | English | |
| Order – Buy | Ηλεκτρονική Μορφή: pdf (10 €) – Digital Type: pdf (10 €)
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| Keywords | Alzheimer’s disease, β-amyloid binding alcohol dehydrogenase (ABAD), pharmacological target. | |
| Other Terms | review article | |
| Summary | Alzheimer’s disease (AD) is the most common neurodegenerative disease and this is the reason why many models have been proposed for its confrontation. Till now, therapy is mainly symptomatic, because the molecular base of the disease involves many biological cell functions. Although the cause of AD is not yet known, it seems that a central role in the pathogenesis of the disease play the β-amyloid proteins (Aβ) that are found in the observed neuritic plaques, whose metabolism and receptors have been set as potential pharmacological targets. β-Amyloid Binding Alcohol Dehydrogenase (ABAD) belongs to the protein family of short chain dehydrogenase/reductases (SDR) and is localized in both endoplasmic reticulum and mitochondria. The biological role of ABAD is to induce cell stress mediated by Aβ. Its distinctiveness is that it binds Aβ in nanomolar range and is involved in many metabolic pathways demonstrating enzymatic activity toward a broad array of substrates (linear alcohols, 3-hydroxyacyl-CoA derivatives, steroids such as 17β-estradiol). Binding with Aβ causes generation of reactive aldehydes, expression of cell stress markers and suppression of the neuroprotective effect of estrogens. Expression of ABAD is increased in AD brain, especially in neurons near deposits of Aβ and brain regions with ischemia. Structurally, ABAD is mainly characterized by a region in its active site that binds NAD+ (essential for the 3rd stage of the β-oxidation of lipids, where ABAD’s role is crucial). ABAD seems to be indispensable for the cell viability, as in in vivo studies gene inactivation linked to lethal phenotypes and multiple developmental abnormalities. Research till now might have discouraged the pharmacological intervention against ABAD, but the understanding of its contribution to AD pathogenesis could help for its confrontation. | |
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