HemeOxygenase-1: Transducer of Sterol Dys-Regulation in Alzheimer Disease

Abstract

Cholesterol (CH) and oxysterols have been consistently implicated in brain aging, Alzheimer’s disease (AD) and otherhuman neurodegenerative conditions, althoughthe mechanisms underlying these relationships remain poorly understood. Heme oxygenase-1 (HO-1) is a highly-inducible stress protein responsible for the catabolism of heme to free iron, carbon monoxide (CO) and biliverdin/bilirubin. HO-1 mRNA and protein levels are augmented in Alzheimer-diseased neural tissues where they may promote pathological iron deposition and oxidative mitochondrial damage characteristic of this disorder. Here, we review evidence derived from cultured rat astroglia, post-mortem human AD brain samples, novel GFAP. HMOX1 transgenic mice and a triple transgenic AD mouse model (3xTg-AD) implicating HO-1 as a pivotal transducer of noxious ambient stimuli into abnormal patterns of brain sterol/oxysterol homeostasis germane to the pathogenesis of AD and other aging-related neurodegenerative disorders.