Alzheimer's Disease and NQO1: Is there a Link?

Abstract

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterised by a progressive decline in cognitive function and represents a major healthcare challenge worldwide. Increasing evidence indicates that mitochondrial dysfunction mediated oxidative stress plays a significant role in the pathophysiological process of AD. Therefore, the physiological activation of antioxidant enzymes that respond to increased oxidative stress is thought to prevent neuropathology. One of those endogenous defences is NADPH quinone oxidoreductase 1 (NQO1). NQO1 is a cytosolic homodimeric flavoprotein that catalyses the two-electron reduction of quinones and related molecules aimed at increasing their solubility and excretion. In line with its role as a phase II stress response protein, altered NQO1 expression is associated with several pathological conditions and disorders including AD. Conclusion: This review summarizes the association between NQO1 and AD pathology. Understanding this association will provide further insight into the pathogenesis of the disease. More importantly, recent interest in drugs that affect NQO1 expression or its activity provides hope that this approach could lead to novel therapeutic options for the treatment of AD.