2007 issue 1

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Volume 16, issue 1

Review article

Amyloid beta peptide toxicity and oxidative stress in the pathogenesis of Alzheimer’s disease

Tadeusz Pietras1
1. Pracownia Gerontologii Kliniki Pneumonologii i Alergologii Uniwersytetu Medycznego w Łodzi
Postępy Psychiatrii i Neurologii 2007; 16 (1): 69-73
Keywords: dementia, amyloid beta, oxidative stress, NADPH oxidase

Abstract

Objectives. Alzheimer 's disease is characterized by the formation of plaques and neurofibrillary tangles around nerve cells. Amyloid beta peptide is the major component of these plaques. This review is aimed at weighing up the evidence that supports both the trophic and toxic properties of amyloid beta peptide.
Review. Amyloid beta protein is the pivotal factor in the pathogenesis of Alzheimer's dementia. In low concentrations the amyloid beta peptide can bind Cu, Zn, and Fe cations, and protect against oxidative stress by inhibiting Fenton's reaction. In high (micromolar) concentrations the amyloid beta peptide undergoes nucleation process and acts as a catalyst participating in the formation of toxic reactive oxygen species such hydrogen peroxide and hydroxyl radical. Moreover, amyloid beta peptide in high concentrations was found to display prooxidative activities of cholesterol oxidase and peroxidase with heme as the prosthetic group. Molecules of amyloid beta peptide activate also strongly prooxidative NADPH oxidase enzyme in granulocytes and microglial cells in the brain via interaction with the neurokinine receptor, Rac protein, and intracellular kinases.
Conclusion. Our conclusion is that amyloid beta peptide under physiological conditions is an important factor of the brain antioxidant system, but when overproduced in Alzheimer's disease it has prooxidative properties, being the source of neuron-damaging reactive oxygen species.

Address for correspondence:
Dr Tadeusz Pietras
Pracownia Gerontologii Kliniki Pneumonologii i Alergologii Uniwersytetu Medycznego
ul. Kopcińskiego 22, 90-153 Łódź
tel. (42) 6787505
fax: (42) 6782129
e-mail: cital200@wp.pl