Curr Alzheimer Res 2008 Dec;5(6):525-32
Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Multiple lines of evidence demonstrate that oxidative stress is an early event in Alzheimer's disease (AD), occurring prior to cytopathology, and therefore may play a key pathogenic role in AD. Oxidative stress not only temporally precedes the pathological lesions of the disease but also activates cell signaling pathways, which, in turn, contribute to lesion formation and, at the same time, provoke cellular responses such as compensatory upregulation of antioxidant enzymes found in vulnerable neurons in AD. In this review, we provide an overview of the evidence of oxidative stress and compensatory responses that occur in AD, particularly focused on potential sources of oxidative stress and the roles and mechanism of activation of stress-activated protein kinase pathways.