title: Oxidative stress and amyloid beta toxicity in Alzheimer's disease: intervention in a complex relationship by antioxidants.
abstract: The elucidation of the intriguing relationship between oxidative stress and Alzheimer's disease is crucial to understand the pathogenesis of the disease as also to design a suitable drug trial with antioxidants against this condition. We begin by reviewing the basic facts about Alzheimer's disease and the chemistry and biology of oxygen free radicals with particular reference to the cellular adaptive response through redox-signalling pathways. The post-mortem evidence of oxidative damage in the brain of Alzheimer's disease patients is overwhelming which is also supported by the similar changes in transgenic mice models of this disease. However, the causal relationship of oxidative stress with amyloid beta pathology or the genesis of Alzheimer's disease is not clear. Considering the available evidence the review suggests that the oxidative stress could be an early event in the disease process and may trigger various adaptive responses such as the alterations of amyloid beta metabolism and the activation of stress responsive kinases which can subsequently lead to neuronal degeneration and AD pathology. Further, we have presented a large body of evidence from various studies to highlight the beneficial effects of antioxidants against amyloid beta toxicity or AD pathology in animal or cell based models of AD. The failure of clinical trials with antioxidants against AD has been mentioned and the possible causes of such failures have been analysed.
authors.affiliation: Department of Biochemistry, Institute of Postgraduate Medical Education and Research, 244, Acharya J.C. Bose Road, Kolkata 700020, India. s_chakrabarti54@yahoo.co.in.
authors.forename: S
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: M
authors.initials: M
authors.lastname: Sinha
authors.forename: I G
authors.initials: IG
authors.lastname: Thakurta
authors.forename: P
authors.initials: P
authors.lastname: Banerjee
authors.forename: M
authors.initials: M
authors.lastname: Chattopadhyay
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008670:Metals; D017382:Reactive Oxygen Species; D004247:DNA