Keywords: Alzheimer, S Disease, Copper, Nerve Growth Factor, Peptide, Zinc, Copper Ion, Inorganic Compound, Metal Ion, Neurotrophic Factor, Zinc Ion, Alzheimer Disease, Brain Region, Homeostasis, Human, Metal Metabolism, Metallostasis, Nerve Degeneration, Nonhuman, Protein Function, Protein Homeostasis, Protein Interaction, Review, Brain-Derived Neurotrophic Factor, Neurotrophin 3, Protein Binding, Protein Conformation,
Affiliations: *** IBB - CNR ***
Dipartimento di Scienze Chimiche, Universita degli Studi di Catania, Viale Andrea Doria 6, Catania, Italy.
Istituto di Biostrutture e Bioimmagini-CNR-Catania, Viale Andrea Doria 6, 95125 Catania, Italy
Scuola Superiore di Catania, Via Valdisavoia 9, 95123 Catania, Italy
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The inorganic perspectives of neurotrophins and Alzheimer's disease
The recent metal hypothesis represents an attempt of a new interpretation key of Alzheimer's disease (AD) to overcome the limits of amyloid cascade. Neurons need to maintain metal ions within a narrow range of concentrations to avoid a detrimental alteration of their homeostasis, guaranteed by a network of specific metal ion transporters and chaperones. Indeed, it is well known that transition metal ions take part in neuromodulation/neurotrasmission. In addition, they are prominent factors in the development and exacerbation of neurodegeneration. Neurotrophins are proteins involved in development, maintenance, survival and synaptic plasticity of central and peripheral nervous systems. A neurotrophin hypothesis of AD has been proposed, whereas the link between neurotrophic factor, the amyloid cascade and biometals has not been taken into account. As a matter of fact, there is a significant overlap between brain areas featured by metal ion dys-homeostasis, and those where the neurotrophins exert their biological activity. Metal ions can directly modulate their activities, through conformational changes, and/or indirectly by activating their downstream signaling in a neurotrophin-independent mode. The focus of this review is on the molecular aspects of Zn(2+) and Cu(2+) interactions with neurotrophins, with the aim to shed light on the intricate mechanisms involving metallostasis and proteostasis in AD. Copyright 2011 Elsevier Inc. All rights reserved.
The inorganic perspectives of neurotrophins and Alzheimer's disease
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Bruni AC, Bernardi L, Colao R, Rubino E, Smirne N, Frangipane F, Terni B, Curcio SA, Mirabelli M, Clodomiro A, Di Lorenzo R, Maletta R, Anfossi M, Gallo M, Geracitano S, Tomaino C, Muraca MG, Leotta A, Lio SG, Pinessi L, Rainero I, Sorbi S, Nee L, Milan G, Pappata S, Postiglione A, Abbamondi N, Forloni G, St George Hyslop P, Rogaeva E, Bugiani O, Giaccone G, Foncin JF, Spillantini MG, Puccio G * Worldwide distribution of PSEN1 Met146Leu mutation: A large variability for a founder mutation(849 views) Neurology (ISSN: 0028-3878, 1526-632x, 1526-632xelectronic), 2010 Mar 9; 74(10): 798-806. Impact Factor:8.017 ViewExport to BibTeXExport to EndNote