Copper in disorders with neurological symptoms: Alzheimer’s, Menkes, and Wilson diseases

• Published in: Brain research bulletin Vol. 55; no. 2; pp. 175 - 185
• Main Authors: Strausak, Daniel, Mercer, Julian F.B, Dieter, Hermann H, Stremmel, Wolfgang, Multhaup, Gerd
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 15.05.2001; Elsevier Science
• Subjects: Alzheimer Disease - enzymology; Alzheimer Disease - genetics; Alzheimer Disease - physiopathology; Alzheimer’s disease; Animals; Biological and medical sciences; Brain - enzymology; Brain - pathology; Brain - physiopathology; Copper; Copper - metabolism; copper-binding protein; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Enzymes - metabolism; Hepatolenticular Degeneration - enzymology; Hepatolenticular Degeneration - genetics; Hepatolenticular Degeneration - physiopathology; Homeostasis - physiology; Humans; Medical sciences; Menkes; Menkes Kinky Hair Syndrome - enzymology; Menkes Kinky Hair Syndrome - genetics; Menkes Kinky Hair Syndrome - physiopathology; Metalloproteins - metabolism; Nerve Degeneration - genetics; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neurodegeneration; Neurology; Wilson; Wilson; Menkes; Alzheimer’s disease; Copper; Neurodegeneration; Skin disease; Nervous system diseases; Wilson disease; Alzheimer disease; Metabolic diseases; Review; Inorganic element; Enzymopathy; Cerebral disorder; Genetic disease; Central nervous system disease; Menkes syndrome; Degenerative disease
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/S0361-9230(01)00454-3

Copper is an essential element for the activity of a number of physiologically important enzymes. Enzyme-related malfunctions may contribute to severe neurological symptoms and neurological diseases: copper is a component of cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide-dismutase which plays a key role in the cellular response to oxidative stress by scavenging reactive oxygen species. Furthermore, copper is a constituent of dopamine-β-hydroxylase, a critical enzyme in the catecholamine biosynthetic pathway. A detailed exploration of the biological importance and functional properties of proteins associated with neurological symptoms will have an important impact on understanding disease mechanisms and may accelerate development and testing of new therapeutic approaches. Copper binding proteins play important roles in the establishment and maintenance of metal-ion homeostasis, in deficiency disorders with neurological symptoms (Menkes disease, Wilson disease) and in neurodegenerative diseases (Alzheimer’s disease). The Menkes and Wilson proteins have been characterized as copper transporters and the amyloid precursor protein (APP) of Alzheimer’s disease has been proposed to work as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological observations in neurodegenerative disorders like Alzheimer’s disease and in the genetically inherited copper-dependent disorders Menkes and Wilson disease are summarized. This could provide a rationale for a link between severely dysregulated metal-ion homeostasis and the selective neuronal pathology.