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- Title
Redox active iron accumulation in aceruloplasminemia.
- Authors
Gonzalez-Cuyar, Luis F.; Perry, George; Miyajima, Hiroaki; Atwood, Craig S.; Riveros-Angel, Marcela; Lyons, Patrick F.; Siedlak, Sandra L.; Smith, Mark A.; Castellani, Rudy J.
- Abstract
Aceruloplasminemia is an autosomal recessive disorder characterized by a ceruloplasmin gene mutation and defective or absent ceruloplasmin function. Because ceruloplasmin functions in iron transport and storage, aceruloplasminemia leads to excessive iron accumulation systemically and within the CNS. The type and form of iron deposited is unclear and while oxidative stress was hypothesized as a potential mechanism of cytotoxicity in this disorder, direct evidence linking oxidative stress to the underlying genetic defect has not been provided. To address these issues, we studied autopsy brain tissue from two subjects with genetically confirmed aceruloplasminemia using an assay developed in our laboratory for redox-active iron assessment. We found iron deposited in perivascular areas, localizing to terminal astrocytic processes and further showed that this iron was redox active. These data are consistent with the concept that oxidative stress, driven by heavy metal accumulation, represents the primary cellular cytotoxic process, accounting for neuronal damage in affected brain regions. As such, aceruloplasminemia is an excellent model of transition metal-driven oxidative stress and neurodegeneration.
- Subjects
CERULOPLASMIN; IRON in the body; CENTRAL nervous system abnormality genetics; CENTRAL nervous system diseases; OXIDATIVE stress; GENETICS
- Publication
Neuropathology, 2008, Vol 28, Issue 5, p466
- ISSN
0919-6544
- Publication type
Article
- DOI
10.1111/j.1440-1789.2008.00901.x