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Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders.
Ann N Y Acad Sci 2004; 1012:37-50AN

Abstract

Membrane lipid peroxidation and oxidative modification of various membrane and associated proteins (e.g., receptors, ion transporters and channels, and signal transduction and cytoskeletal proteins) occur in a range of neurodegenerative disorders. This membrane-associated oxidative stress (MAOS) is promoted by redox-active metals, most notably iron and copper. The mechanisms whereby different genetic and environmental factors initiate MAOS in specific neurological disorders are being elucidated. In Alzheimer's disease (AD), the amyloid beta-peptide generates reactive oxygen species and induces MAOS, resulting in disruption of cellular calcium homeostasis. In Parkinson's disease (PD), mitochondrial toxins and perturbed ubiquitin-dependent proteolysis may impair ATP production and increase oxyradical production and MAOS. The inheritance of polyglutamine-expanded huntingtin may promote neuronal degeneration in Huntington's disease (HD), in part, by increasing MAOS. Increased MAOS occurs in amyotrophic lateral sclerosis (ALS) as the result of genetic abnormalities (e.g., Cu/Zn-superoxide dismutase mutations) or exposure to environmental toxins. Levels of iron are increased in vulnerable neuronal populations in AD and PD, and dietary and pharmacological manipulations of iron and copper modify the course of the disease in mouse models of AD and PD in ways that suggest a role for these metals in disease pathogenesis. An increasing number of pharmacological and dietary interventions are being identified that can suppress MAOS and neuronal damage and improve functional outcome in animal models of AD, PD, HD, and ALS. Novel preventative and therapeutic approaches for neurodegenerative disorders are emerging from basic research on the molecular and cellular actions of metals and MAOS in neural cells.

Authors+Show Affiliations

Laboratory of Neurosciences, National Institute on Aging Intramural Research Program, and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA. mattsonm@grc.nia.nih.gov

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

15105254

Citation

Mattson, Mark P.. "Metal-catalyzed Disruption of Membrane Protein and Lipid Signaling in the Pathogenesis of Neurodegenerative Disorders." Annals of the New York Academy of Sciences, vol. 1012, 2004, pp. 37-50.
Mattson MP. Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Ann N Y Acad Sci. 2004;1012:37-50.
Mattson, M. P. (2004). Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Annals of the New York Academy of Sciences, 1012, pp. 37-50.
Mattson MP. Metal-catalyzed Disruption of Membrane Protein and Lipid Signaling in the Pathogenesis of Neurodegenerative Disorders. Ann N Y Acad Sci. 2004;1012:37-50. PubMed PMID: 15105254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. A1 - Mattson,Mark P, PY - 2004/4/24/pubmed PY - 2004/5/20/medline PY - 2004/4/24/entrez SP - 37 EP - 50 JF - Annals of the New York Academy of Sciences JO - Ann. N. Y. Acad. Sci. VL - 1012 N2 - Membrane lipid peroxidation and oxidative modification of various membrane and associated proteins (e.g., receptors, ion transporters and channels, and signal transduction and cytoskeletal proteins) occur in a range of neurodegenerative disorders. This membrane-associated oxidative stress (MAOS) is promoted by redox-active metals, most notably iron and copper. The mechanisms whereby different genetic and environmental factors initiate MAOS in specific neurological disorders are being elucidated. In Alzheimer's disease (AD), the amyloid beta-peptide generates reactive oxygen species and induces MAOS, resulting in disruption of cellular calcium homeostasis. In Parkinson's disease (PD), mitochondrial toxins and perturbed ubiquitin-dependent proteolysis may impair ATP production and increase oxyradical production and MAOS. The inheritance of polyglutamine-expanded huntingtin may promote neuronal degeneration in Huntington's disease (HD), in part, by increasing MAOS. Increased MAOS occurs in amyotrophic lateral sclerosis (ALS) as the result of genetic abnormalities (e.g., Cu/Zn-superoxide dismutase mutations) or exposure to environmental toxins. Levels of iron are increased in vulnerable neuronal populations in AD and PD, and dietary and pharmacological manipulations of iron and copper modify the course of the disease in mouse models of AD and PD in ways that suggest a role for these metals in disease pathogenesis. An increasing number of pharmacological and dietary interventions are being identified that can suppress MAOS and neuronal damage and improve functional outcome in animal models of AD, PD, HD, and ALS. Novel preventative and therapeutic approaches for neurodegenerative disorders are emerging from basic research on the molecular and cellular actions of metals and MAOS in neural cells. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/15105254/Metal_catalyzed_disruption_of_membrane_protein_and_lipid_signaling_in_the_pathogenesis_of_neurodegenerative_disorders_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2004&volume=1012&spage=37 DB - PRIME DP - Unbound Medicine ER -