Alterations of the homeostasis of the transition metal copper in neurodegenerative disorders.

Brain, like all biological systems, contains an intricate protein apparatus to perform the accurate control of the distribution and reactivity of the transition metal copper, a janus-faced element, which combines essentiality and potential toxicity. The notion that both the genetic diseases associated with the impairment of copper transporters, Menkes’ and Wilson’s diseases, show neurodegeneration lead to the proposal that the alteration of copper homeostasis might be implicated in degenerative pathologies of brain. The discovery of novel crucial roles for copper in brain function and the copperbinding properties of proteins (amyloid precursor protein, prion protein, synuclein, huntingtin) gives support to this hypothesis and opened new research areas. Here we will describe the mechanisms underlying neurodegeneration in the acknowledged genetic disturbances of copper homeostasis, as well as the possible involvement of copper in the aetiology of many neurodegenerative disease of the brain (Alzheimer’s, familial amyotrophic lateral sclerosis, Hungtinton’s, Parkinson’s and prion diseases).