Current Medicinal Chemistry - Central Nervous System Agents

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Alzheimers Disease and Oxidative Stress: The Old Problem Remains Unsolved

Author(s): Paula I. Moreira, Kazuhiro Honda, Quan Liu, Gjumrakch Aliev, Catarina R. Oliveira, Maria S. Santos, Xiongwei Zhu, Mark A. Smith, George Perry.

Abstract:

Despite the controversial discussion about amyloid-β as a cause or consequence of Alzheimer disease pathophysiology, one of the most devastating neurodegenerative disorders, all researchers working in this field agree that oxidative stress is intimately associated with Alzheimer disease. This review will focus primarily on oxidative stress associated to disturbances in energy metabolism, with special emphasis on the role of mitochondrial dysfunction and the overproduction of reactive oxygen and nitrogen species. These free radical species attack neuronal lipids, proteins and nucleic acids inevitably leading to neuronal dysfunction. These neuronal alterations can be measured using several markers such as protein carbonyls and 3-nitrotyrosine (protein oxidation markers), malondialdehyde, thiobarbituric acid-reactive substances, 4-hydroxynonenal and acrolein (lipid oxidation markers), 8-hydroxyguanosine and 8-hydroxy-2-deoxyguanosine (nucleic acid oxidation markers) and advanced glycation end products (glyco-oxidation marker). The prompt identification of early signs of oxidative stress and its potential neuronal targets can open a window for the development of new therapeutic strategies envisaged to prevent or, at least, ameliorate the symptoms of Alzheimer disease. In this line, and since oxidative damage occurs due to an imbalance between reactive species production and cell antioxidant defenses, we will discuss in brief the use of antioxidant-based therapies and their effects in the fight against the oxidative stress occurring in Alzheimer disease.

Keywords: alzheimer disease, antioxidants, apoptosis, mitochondria, oxidative stress

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Article Details

VOLUME: 5
ISSUE: 1
Year: 2005
Page: [51 - 62]
Pages: 12
DOI: 10.2174/1568015053202714