Copper handling by astrocytes: Insights into neurodegenerative diseases

Copper (Cu) is an essential trace element in the brain that can be toxic at elevated levels. Cu accumulation is a suspected etiology in several neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and prion-induced disorders. Astrocytes are a proposed depot in the brain for Cu and other metals, including lead (Pb). This article describes the physiological roles of Cu in the central nervous system and in selected neurodegenerative diseases, and reviews evidence that astrocytes accumulate Cu and protect neurons from Cu toxicity. Findings from murine genetic models of Menkes disease and from cell culture models concerning the molecular mechanisms by which astrocytes take up, store, and buffer Cu intracellularly are discussed, as well as potential mechanistic linkages between astrocyte functions in Cu handling and neurodegenerative diseases.

► Astrocytes serve as a Cu depot for the brain, distribute Cu to neurons, and protect neurons from Cu toxicity.
► Cu dyshomeostasis occurs in Alzheimer's disease Parkinson's disease and other disorders of the brain.
► Cu-handling by astrocytes may contribute to the biochemical pathology of several neurodegenerative diseases.