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NF-κB-regulated, proinflammatory miRNAs in Alzheimer's disease
© 2012 BioMed Central Ltd
Abundant neurochemical, neuropathological, and genetic evidence suggests that a critical number of proinflammatory and innate immune system-associated factors are involved in the underlying pathological pathways that drive the sporadic Alzheimer's disease (AD) process. Most recently, a series of epigenetic factors - including a select family of inducible, proinflammatory, NF-κB-regulated small noncoding RNAs called miRNAs - have been shown to be significantly elevated in abundance in AD brain. These upregulated miRNAs appear to be instrumental in reshaping the human brain transcriptome. This reorganization of mRNA speciation and complexity in turn drives proinflammatory and pathogenic gene expression programs. The ensuing, progressively altered immune and inflammatory signaling patterns in AD brain support immunopathogenetic events and proinflammatory features of the AD phenotype. This report will briefly review what is known concerning NF-κB-inducible miRNAs that are significantly upregulated in AD-targeted anatomical regions of degenerating human brain cells and tissues. Quenching of NF-κB-sensitive inflammatory miRNA signaling using NF-κB-inhibitors such as the polyphenolic resveratrol analog trans-3,5,4'-trihydroxystilbene (CAY10512) may have some therapeutic value in reducing inflammatory neurodegeneration. Antagonism of NF-κB-inducing, and hence proinflammatory, epigenetic and environmental factors, such as the neurotrophic herpes simplex virus-1 and exposure to the potent neurotoxin aluminum, are briefly discussed. ...
J Inorg Biochem. 2010 Sep;104(9):1010-2. Evidence supporting a biological role for aluminum in chromatin compaction and epigenetics.
Averaging 8.1% (w/w) of the earth's crust, aluminum is the most highly abundant metal in our biosphere, yet has long been thought to serve no essential biological function. In aqueous solutions, aluminum salts and hydroxides are exceptionally potent aggregators of biological molecules, often coalescing molecular species to the point that they precipitate out of solution. A biological function for aluminum is proposed in which this abundant, high charge density metal cation has a significant role in biomolecular compaction. Sometimes, molecules ectopically aggregated by aluminum are associated with pathological conditions. The data further suggests that a specific consequence of 'aluminum biocompaction' may be particularly important in the condensation of A+T-rich chromatin domains, and in silencing the expression of specific kinds of genetic information.