Metal dyshomeostasis and inflammation in Alzheimer's and Parkinson's diseases: possible impact of environmental exposures.

ABSTRACT: 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 importa

SUBMITTER: Myhre O 

PROVIDER: S-EPMC3654362 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature