Possible Prevention of Alzheimer芒聙聶s Disease by Aldehyde Dehydrogenase: A Perspective Review
*Corresponding Author: Tetsumori Yamashima, Department of Psychiatry and Behavioral Science and Cell Metabolism and Nutrition, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan, Tel: +81-9021291429, Fax: +81-762471338, Email: yamashima215@gmail.comReceived Date: Mar 19, 2020 / Accepted Date: Jun 04, 2020 / Published Date: Jun 11, 2020
Citation: Yamashima T (2020) Possible Prevention of Alzheimer’s Disease by Aldehyde Dehydrogenase: A Perspective Review. J Alzheimers Dis Parkinsonism 10:489.
Copyright: © 2020 Yamashima T. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Investigating the mechanism of neuronal death in Alzheimer’s disease is difficult, because only a tiny percentage of neurons are degenerating at any time point during the long prodromal period. Epidemiological, genetic, biochemical and animal model studies have attributed excessive aldehyde load as a cause of Alzheimer neuronal death. Focusing on toxic aldehydes will help fill gaps in our knowledge that cannot be explained by the amyloid β or tau hypotheses. Hydroxynonenal is formed by peroxidation of membrane lipids and LDL or during deep-frying of vegetable oils. It carbonylates Hsp70.1, a heat shock protein with the dual functions of a chaperone protein and lysosomal stabilizer. Hydroxynonenal-mediated Hsp70.1 carbonylation followed by calpain-mediated cleavage of carbonylated Hsp70.1, causes lysosomal neuronal death (the ‘calpain-cathepsin hypothesis’). Aldehyde dehydrogenase (ALDH) participates in the removal of not only ethanol-derived acetaldehyde, but also linoleic acid-derived hydroxynonenal. This review describes how scavenging hydroxynonenal by ALDH enzymes prevent Alzheimer’s disease.
