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Alzheimer's disease, metal ions and metal homeostatic therapy.

Abstract

Mounting evidences support the idea that endogenous 'biometals', such as copper, iron, zinc and exogenous ones such as aluminum, can be involved as factors or cofactors in the etiopathogenesis of a variety of neurodegenerative diseases. Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. In AD, the process of beta-amyloid (Abeta) misfolding and plaque aggregation is greatly influenced by alterations in the homeostasis of the aforementioned metal ions. Here, we discuss the most recent evidences that associate metal ion dyshomeostasis with the development of AD. As for aluminum, a role for this ion in AD pathogenesis is still controversial. Thus, here, we also critically review new findings that argue for and against the 'aluminum hypothesis'. Finally, it is discussed how therapeutic strategies aimed at restoring metal homeostasis can delay and modify the progression of AD-related neurodegeneration.

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  • Authors+Show Affiliations

    ,

    CNR-Institute for Biomedical Technologies, Padua 'Metalloproteins' Unit, Department of Biology, University of Padua, Viale G. Colombo 3-35121 Padua, Italy. zatta@mail.bio.unipd.it

    , ,

    Source

    Trends in pharmacological sciences 30:7 2009 Jul pg 346-55

    MeSH

    Alzheimer Disease
    Animals
    Clioquinol
    Homeostasis
    Humans
    Metals
    Plaque, Amyloid

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    19540003

    Citation

    Zatta, Paolo, et al. "Alzheimer's Disease, Metal Ions and Metal Homeostatic Therapy." Trends in Pharmacological Sciences, vol. 30, no. 7, 2009, pp. 346-55.
    Zatta P, Drago D, Bolognin S, et al. Alzheimer's disease, metal ions and metal homeostatic therapy. Trends Pharmacol Sci. 2009;30(7):346-55.
    Zatta, P., Drago, D., Bolognin, S., & Sensi, S. L. (2009). Alzheimer's disease, metal ions and metal homeostatic therapy. Trends in Pharmacological Sciences, 30(7), pp. 346-55. doi:10.1016/j.tips.2009.05.002.
    Zatta P, et al. Alzheimer's Disease, Metal Ions and Metal Homeostatic Therapy. Trends Pharmacol Sci. 2009;30(7):346-55. PubMed PMID: 19540003.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Alzheimer's disease, metal ions and metal homeostatic therapy. AU - Zatta,Paolo, AU - Drago,Denise, AU - Bolognin,Silvia, AU - Sensi,Stefano L, Y1 - 2009/06/17/ PY - 2009/01/30/received PY - 2009/04/15/revised PY - 2009/05/06/accepted PY - 2009/6/23/entrez PY - 2009/6/23/pubmed PY - 2011/8/4/medline SP - 346 EP - 55 JF - Trends in pharmacological sciences JO - Trends Pharmacol. Sci. VL - 30 IS - 7 N2 - Mounting evidences support the idea that endogenous 'biometals', such as copper, iron, zinc and exogenous ones such as aluminum, can be involved as factors or cofactors in the etiopathogenesis of a variety of neurodegenerative diseases. Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. In AD, the process of beta-amyloid (Abeta) misfolding and plaque aggregation is greatly influenced by alterations in the homeostasis of the aforementioned metal ions. Here, we discuss the most recent evidences that associate metal ion dyshomeostasis with the development of AD. As for aluminum, a role for this ion in AD pathogenesis is still controversial. Thus, here, we also critically review new findings that argue for and against the 'aluminum hypothesis'. Finally, it is discussed how therapeutic strategies aimed at restoring metal homeostasis can delay and modify the progression of AD-related neurodegeneration. SN - 1873-3735 UR - https://www.unboundmedicine.com/medline/citation/19540003/Alzheimer's_disease_metal_ions_and_metal_homeostatic_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-6147(09)00088-1 DB - PRIME DP - Unbound Medicine ER -