The neurotoxicity of iron, copper and manganese in Parkinson's and Wilson's diseases

Contribution of metals to brain MR signal intensity: review articles

“…Copper metabolic abnormalities include Wilson's disease, which is a condition associated with excessive copper accumulation, and Menkes disease, which is a condition related to copper deficiency [87][88][89][90]. Wilson's disease is caused by a mutation in the gene for ATP7B, which binds copper to ceruloplasmin and facilitates the excretion of the copper-ceruloplasmin complex in the bile; the mutation leads to the gradual accumulation of copper in the body [89][90][91]. It is known that copper has a relatively small paramagnetic effect on MRI [92,93] and that, on its own, copper accumulation does not directly cause signal intensity changes [91].…”

“…Wilson's disease is caused by a mutation in the gene for ATP7B, which binds copper to ceruloplasmin and facilitates the excretion of the copper-ceruloplasmin complex in the bile; the mutation leads to the gradual accumulation of copper in the body [89][90][91]. It is known that copper has a relatively small paramagnetic effect on MRI [92,93] and that, on its own, copper accumulation does not directly cause signal intensity changes [91]. Brain MRI abnormalities in Wilson's disease patients include brain atrophy, symmetric regional hyperintensity on T2WI, hypointensity in basal ganglia on T2WI, and a hyperintense globus pallidus on T1WI [94][95][96].…”

“…Hyperintense regions on T2WI occasionally diminish after therapy, and this change may reflect edema and gliosis [98][99][100]. Hyperintensity of the globus pallidus on T1WI was initially attributed to copper accumulation [101], but manganese deposition due to liver dysfunction has more recently been implicated [91,100]. Hypointensity of the substantia nigra, striatum, and globus pallidus on T2WI is believed to be due to increased accumulation of both copper and iron (Fig.…”

“…Hypointensity of the substantia nigra, striatum, and globus pallidus on T2WI is believed to be due to increased accumulation of both copper and iron (Fig. 3) [91,96,102]. Ceruloplasmin, which transports not only copper but also iron, is decreased in Wilson's disease, and this enhances iron accumulation in the body [89,90].…”

Iron chelation in the treatment of neurodegenerative diseases

“…This observation triggered interest in iron chelation therapy for these disorders [118] (Table 6). In PD, iron levels in the substantia nigra pars compacta (SNpc) are increased by a factor of 1.5-2, but are not altered in other brain regions [119]. This increase can clearly be detected in vivo by MRI when the SNpc is segmented.…”