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.
|Autori:||Travaglia A; Pietropaolo A; La Mendola D; Nicoletti VG; Rizzarelli E|
|Titolo:||The inorganic perspectives of neurotrophins and Alzheimer's disease|
|Anno del prodotto:||2012|
|Digital Object Identifier (DOI):||10.1016/j.jinorgbio.2011.10.017|
|Appare nelle tipologie:||1.1 Articolo in rivista|