Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 111, Issue -, Pages 130-137Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2011.10.017
Keywords
Nerve growth factor; Zinc; Copper; Alzheimer's disease; Peptide
Funding
- MIUR [PRIN 2008 R23Z7K_001]
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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 Zn2+ and Cu2+ interactions with neurotrophins, with the aim to shed light on the intricate mechanisms involving metallostasis and proteostasis in AD. (C) 2011 Elsevier Inc. All rights reserved.
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