Wilson’s Disease: A Comprehensive Review of the Molecular Mechanisms

Abstract

Wilson’s disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder resulting from abnormal copper metabolism. Reduced copper excretion causes an excessive deposition of the copper in many organs such as the liver, central nervous system (CNS), cornea, kidney, joints, and cardiac muscle where the physiological functions of the affected organs are impaired. The underlying molecular mechanisms for WD have been extensively studied. It is now believed that a defect in P-type adenosine triphosphatase (ATP7B), the gene encoding the copper transporting P-type ATPase, is responsible for hepatic copper accumulation. Deposited copper in the liver produces toxic effects via modulating several molecular pathways. WD can be a lethal disease if left untreated. A better understanding of the molecular mechanisms causing the aberrant copper deposition and organ damage is the key to developing effective management approaches.

Maladie de Wilson : présentation d’un cas et revue de la littérature

“…Ce transporteur ATP7B est présent dans le foie, le système nerveux et le rein. Au niveau du foie, il joue deux rôles : un rôle de transport du cuivre vers l'appareil de Golgi où le cuivre va être incorporé à l'apocéruloplasmine pour constituer l'holocéruloplasmine et un rôle dans l'excrétion biliaire du cuivre [10]. La quantité de cuivre intrahépatique régule la localisation intracellulaire de l'ATP7B.…”

Wilson's disease patient with iron metabolism discharge barriers: A case report

“…This is known to be the key gene that leads to copper metabolism discharge barriers (1)(2)(3). Thus, copper accumulates mainly in the liver, kidney, head and retina and causes abnormal liver function, renal dysfunction and degeneration of the nervous system (4,5). Moreover, widespread copper accumulation in the central nervous system results in cognitive decline, extrapyramidal change and also pyramidal dysfunction (6).…”

Does vitamin supplement use reduce serum levels of some heavy metals and/or trace inorganic elements in pregnant women?

“…5 Increased tissue copper level may induce a series of harmful biochemical reactions, including oxidative stress, damaging the structure and integrity of mitochondria, and subsequently leading to cell injury. 6 However, low tissue copper levels impair immune and neurological function. 7 It is well-known that there are two hereditary defects in copper metabolism which result in disorders with severe clinical courses.…”

“…The other condition is Menkes disease, a copper deficiency which results from impaired activity of copper-dependent enzymes and is caused by alterations in the genes encoding the P-type ATPase copper transporters, ATP7A in the target organs, contributing to a neurodegenerative disorder. 6,7 Therefore, if appropriate vitamin supplement (>3 times/ wk) for pregnant women would reduce the serum levels of copper, which has been demonstrated in the current issue of the Journal of Chinese Medical Association, 4 is it possible that the fetus might escape a potentially toxic bioaccumulation of mercury and copper? Of course, the fetus might also be at risk for complications arising from low serum levels of copper in a similar situation.…”