Metal Dyshomeostasis and Inflammation in Alzheimer’s and Parkinson’s Diseases : Possible Impact of Environmental Exposures

A dysregulated metal homeostasis is associated with both Alzheimer’s (AD) and Parkinson’s (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering o...

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Bibliographic Details
Published in:Oxidative medicine and cellular longevity 2013-01, Vol.2013 (2013), p.1-19
Main Authors: Myhre, Oddvar, Utkilen, Hans, Duale, Nur, Brunborg, Gunnar, Hofer, Tim
Format: Article
Language:English
Subjects:
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Animals
Environmental Exposure
Homeostasis
Humans
Inflammation - metabolism
Inflammation - pathology
Metals - metabolism
Parkinson Disease - genetics
Parkinson Disease - metabolism
Parkinson Disease - pathology
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Summary:A dysregulated metal homeostasis is associated with both Alzheimer’s (AD) and Parkinson’s (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering of cortex copper mechanism is suggested. An age-related mild chronic inflammation and/or elevated intracellular iron can trigger hepcidin production followed by its binding to ferroportin which is the only neuronal iron exporter, thereby subjecting it to lysosomal degradation. Subsequently raised neuronal iron levels can induce translation of the ferroportin assisting and copper binding amyloid precursor protein (APP); constitutive APP transmembrane passage lowers the copper pool which is important for many enzymes. Using in silico gene expression analyses, we here show significantly decreased expression of copper-dependent enzymes in AD brain and metallothioneins were upregulated in both diseases. Although few AD exposure risk factors are known, AD-related tauopathies can result from cyanobacterial microcystin and β-methylamino-L-alanine (BMAA) intake. Several environmental exposures may represent risk factors for PD; for this disease neurodegeneration is likely to involve mitochondrial dysfunction, microglial activation, and neuroinflammation. Administration of metal chelators and anti-inflammatory agents could affect disease outcomes.
ISSN:1942-0900
1942-0994
DOI:10.1155/2013/726954