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Are Dopamine, Norepinephrine, and Serotonin Precursors of Biologically Reactive Intermediates Involved in the Pathogenesis of Neurodegenerative Brain Disorders?

  • Chapter
Biological Reactive Intermediates VI

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 500))

Abstract

During the past two or three decades an immense amount of research has been carried out to understand the fundamental molecular mechanisms that underlie the neurotoxicity evoked by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), methamphetamine (MA) and related amphetamine drugs of abuse. The neurotoxicity of MPTP is of particular interest because it not only mimics the symptoms and major pathobiochemical changes that occur in Parkinson’s disease (PD) but also arguably provides the best model of PD in animals (Gerlach et al.,1991; Gerlach and Riederer, 1996; Royland and Langston, 1998). Interest in the neurotoxicity evoked by MA derives not only from the fact that this compound is a widely abused psychoactive drug but in animals it also mimics many of the major pathobiochemical changes that occur in PD (Gerlach and Riederer, 1996) although it is a less selective neurotoxin than MPTP. Transient cerebral ischemia, or ischemia-reperfusion (I-R), can also lead to neurodegeneration although this is even less selective than MA. Nevertheless, there are a rather striking number of similar factors that appear to be key steps in a complex cascade of processes that compromise the neurotoxic mechanisms evoked by MPTP, MA and I-R. In this communication similarities associated with the neurotoxicity evoked by MPTP, MA and I-R will be briefly reviewed. Subsequently, these will be integrated into a working hypothesis for the underlying neurotoxic mechanisms in which one or more of the neurotransmitters dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT; serotonin) are proposed to be the precursors of biologically reactive intermediates in the pathological processes.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019, USA

    Glenn Dryhurst

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  1. Glenn Dryhurst
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Editors and Affiliations

  1. Université René Descartes, Paris, France

    Patrick M. Dansette

  2. Rutgers University and The Environmental & Occupational Health Sciences Institute, Piscataway, New Jersey, USA

    Robert Snyder

  3. CNRS, Paris, France

    Marcel Delaforge

  4. University of Surrey, Guildford, Surrey, England

    G. Gordon Gibson

  5. Institute of Toxicology and Environmental Health, The Technical University of Munich, Munich, Germany

    Helmut Greim

  6. Medical University of South Carolina, Charleston, South Carolina, USA

    David J. Jollow

  7. University of Texas, Austin, Texas, USA

    Terrence J. Monks

  8. University of Arizona, Tucson, Arizona, USA

    I. Glenn Sipes

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© 2001 Springer Science+Business Media New York

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Dryhurst, G. (2001). Are Dopamine, Norepinephrine, and Serotonin Precursors of Biologically Reactive Intermediates Involved in the Pathogenesis of Neurodegenerative Brain Disorders?. In: Dansette, P.M., et al. Biological Reactive Intermediates VI. Advances in Experimental Medicine and Biology, vol 500. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0667-6_61

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  • DOI: https://doi.org/10.1007/978-1-4615-0667-6_61

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5185-6

  • Online ISBN: 978-1-4615-0667-6

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