Journal de la maladie d'Alzheimer et du parkinsonisme

Abstrait

Possible Prevention of Alzheimer?s Disease by Aldehyde Dehydrogenase: A Perspective Review

Tetsumori Yamashima

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.