Crosstalk between metals and neurodegenerative diseases

Abstract

Trace elements including iron, zinc, copper, and manganese play essential roles in the maintenance of brain functions. Accumulating evidence suggests that dyshomeostasis of trace elements is implicated in the pathogenesis of neurodegenerative diseases including Alzheimer's disease, vascular type of dementia, prion diseases, and dementia with Lewy bodies. These diseases share similarity in the formation of β-sheets containing amyloid fibrils from disease-associated proteins, including the β-amyloid protein (AβP), the prion protein, α-synuclein, and polyglutamine, and the introduction of apoptotic degeneration. Trace elements can bind to these proteins and cause their conformational changes. Furthermore, these proteins reportedly play crucial roles in the regulation of trace elements. Considering that these proteins colocalize in synapses, it is possible that the interactions between the disease-associated proteins and trace elements are based on the physiological roles of these proteins. We review here the current understanding of the pathology of neurodegenerative diseases based on metal binding to disease-associated proteins and on the disruption of metal homeostasis.