title: The inorganic perspectives of neurotrophins and Alzheimer's disease.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Catania, Viale Andrea Doria 6, Catania, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Travaglia
authors.forename: Adriana
authors.initials: A
authors.lastname: Pietropaolo
authors.forename: Diego
authors.initials: D
authors.lastname: La Mendola
authors.forename: Vincenzo Giuseppe
authors.initials: VG
authors.lastname: Nicoletti
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000737:chemistry / Q000378:metabolism; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020932:Nerve Growth Factor / Q000737:chemistry / Q000378:metabolism; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D003300:Copper; D020932:Nerve Growth Factor; D015032:Zinc; C073922:neurotrophin 4