During upregulation of inflammatory processes in the CNS and retina there appears to be things a significant parallel upregulation of the dimeric DNA-binding protein NF-??B (as the p50/p65 complex) [40-48]. Indeed, originally described in 1986, NF-??B has emerged as a ubiquitous transcription factor that controls diverse biological functions including inflammatory and immune functions in both the central and peripheral nervous systems [40-45]. NF-??B may be singularly important in regulating genetic responses to nervous system stress through the innate immune response because it belongs to the category of pre-existing primary transcription factors that are already present in cells in an inactive-sensory state and do not require new protein synthesis to be activated [40-45].

That the NF-??B p50 and p65 subunits belong to an expanding family of more than 25 NF-??B subunits indicates that the subunit composition of NF-??B is variable and may be tailored by the cell to accommodate various inflammatory signaling needs [40,41,44-49]. Interestingly, compared with interleukin-1 receptor-associated kinase (IRAK)-1, the more chronic and persistent activation of the NF-??B p50/p65 complex via the IRAK-2 signaling pathway in AD has recently been described [49]. Importantly, NF-??B activation and binding in the promoters of NF-??B-sensitive genes, including miRNA precursors (see below), leads to the facilitated transcription of many hundreds of potentially pathogenic genes, and therefore has the capacity to completely overwhelm the cell’s anti-oxidant and anti-inflammatory defenses while at the same time altering the functional properties of nervous system cells [40-49].

Speciation, bioactivity and complexity of miRNA in the human brain The potential contribution of small, noncoding RNA to human brain genetic function has been known for at least 20 years [50], but more recently there has been a virtual explosion into molecular-genetic research involving the neurobiological function of small, noncoding RNA and miRNA in brain development, injury, aging, health and disease [38,49,51-59]. Indeed, both small, noncoding RNAs and miRNAs are acquiring increasingly important roles in modulating the pathogenesis of progressive human neurologic disorders including inflammatory neurodegeneration, AD, Down’s syndrome, epileptogenesis, glioma and glioblastoma, human prion diseases such as Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker syndrome, viral infection and aluminum intoxication of the brain, as well in murine Tg-AD and other transgenic models for progressive human neuro-degenerative disorders Batimastat [52-60].

The miRNAs represent an evolutionarily conserved class of single-stranded small, noncoding RNAs averaging approximately 21 to 24 ribonucleotides in sellckchem length.