Oxidative Mediated Neurodegeneration in Alzheimers Disease: Melatonin and Related Indoles as Neuroprotective Agents

Author(s): M. A. Pappolla, R. J. Reiter, T. K. Bryant-Thomas, B. Poeggeler.

Journal Name: Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents

Volume 3 , Issue 1 , 2003

Abstract:

Many of the recent advances in AD stem from the study of a 40-42 amino acid peptide called the amyloid beta protein (Aβ), as the essential pathologic marker of the disorder [1-2]. Our studies and those of others have shown that Aβ is central to the process of neurodegeneration in AD by initiating the production of partially reduced oxygen species and damaging essential macromolecules in the CNS. A growing body of literature links these destructive oxidative processes with some neurodegenerative aspects of AD. Herein we discuss the evidence that melatonin and related indoles can be use as potential therapeutic agents in Alzheimers disease (AD). The principal findings related to the free radical scavenging and antioxidative properties of melatonin in various paradigms of AD are presented. The hormone efficacy and the likely mechanisms involved in its ability to reduce neuronal damage mediated by oxygen-based reactive species in AD models of neurodegeneration are discussed. We will discuss the experimental data suggesting that besides the direct scavenging properties and indirect antioxidant actions of melatonin, its ability to protect neurons probably also stems from novel antiamyloidogenic properties of the hormone. Melatonin is also unique because of the ease with which it passes through the blood-brain barrier and has distinct physiological relationships to the aging process. A brief introductory discussion on the biology and neuropathology of AD is offered with a consideration of the relationship between free radicals and the pathogenesis of the disease.

Keywords: Oxidative Mediated, Neurodegeneration, Neuroprotective Agents

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Article Details

VOLUME: 3
ISSUE: 1
Year: 2003
Page: [33 - 46]
Pages: 14
DOI: 10.2174/1568013033358707

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