Two Abstracts About Oxidative Stress & Alzheimer's Disease

Abstract:

Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal

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Domenico Praticò
Department of Pharmacology, Temple University, School of Medicine, Philadelphia, PA 19140, USA

Available online

Alzheimer’s disease (AD) is the most common form of neurodegenerative disorder with dementia. In its sporadic form, AD results from the combination of genetic factors with different epigenetic events. Among them, oxidative metabolic reactions and their by-products have been consistently implicated in AD pathogenesis and represent the biological basis for the ‘oxidative stress hypothesis of AD. Numerous studies demonstrate that different biomarkers of oxidative-stress-mediated events are elevated in the AD brain. Studies in animal models of the disease with antioxidants report significant improvements of their AD-like phenotype. Although epidemiologic studies show that dietary intake of antioxidants reduces the risk of AD, clinical trials with antioxidants show only a marginal positive or no effect. These conflicting results have created a wave of criticism towards the oxidative stress hypothesis of AD. Here, I review the available data and discuss the necessary paths for a fair reappraisal of the hypothesis.

Abstract:

Serial review: causes and consequences of oxidative stress in Alzheimer’s disease

Antioxidant neuroprotection in Alzheimer’s disease as preventive and therapeutic approach

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Christian Behland Bernd Moosmann

Max Planck Institute of Psychiatry, Munich, Germany

Received 6 February 2002; 

accepted 18 April 2002. 

Available online

Abstract

Various neurodegenerative disorders and syndromes are associated with oxidative stress. The deleterious consequences of excessive oxidations and the pathophysiological role of reactive oxygen species (ROS) have been intensively studied in Alzheimer’s disease (AD). Neuronal cell dysfunction and oxidative cell death caused by the AD-associated amyloid β protein may causally contribute to the pathogenesis of AD. Antioxidants that prevent the detrimental consequences of ROS are consequently considered to be a promising approach to neuroprotection. While there is ample experimental evidence demonstrating neuroprotective activities of antioxidants in vitro, the clinical evidence that antioxidant compounds act as protective drugs is still relatively scarce. Nevertheless, antioxidants constitute a major part of the panel of clinical and experimental drugs that are currently considered for AD prevention and therapy. Here, focus is put mainly on phenolic antioxidant structures that belong to the class of direct antioxidants. Experimental and clinical evidence for the neuroprotective potential of α-tocopherol (vitamin E) and 17β-estradiol (estrogen) is shortly summarized and an outlook is given on possible novel antioxidant lead structures with improved pharmacological features.
Author Keywords: Alzheimer’s disease; Antioxidant; Estrogen; Free radical; Neuroprotection; Oxidative stress; Phenol; Tocopherol
Abbreviations: AD, Alzheimer’s disease; Aβ, amyloid β protein; ACh, acetylcholine; AGEs, advanced glycation endproducts; APP, Aβ precursor protein; ROS, reactive oxygen species; TMP, 2,4,6-trimethylphenol; THC, (−)Δ⁹-tetrahydrocannabinol