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

摘要: A dysregulated metal homeostasis is associated with both Alzheimer's (AD) and Parkinson's (PD) diseases; AD patients have decreased cortex elevated serum copper levels along extracellular amyloid-beta plaques containing copper, iron, zinc. For AD, a putative hepcidin-mediated lowering of mechanism suggested. An age-related mild chronic inflammation and/or intracellular iron can trigger hepcidin production followed by its binding to ferroportin which the only neuronal exporter, thereby subjecting it lysosomal degradation. Subsequently raised induce translation assisting amyloid precursor protein (APP); constitutive APP transmembrane passage lowers pool important for many enzymes. Using in silico gene expression analyses, we here show significantly copper-dependent enzymes brain metallothioneins were upregulated diseases. Although few exposure risk factors are known, AD-related tauopathies result from cyanobacterial microcystin β-methylamino-L-alanine (BMAA) intake. Several environmental exposures may represent PD; this disease neurodegeneration likely involve mitochondrial dysfunction, microglial activation, neuroinflammation. Administration chelators anti-inflammatory agents could affect outcomes.