title: Oxidative stress and pro-inflammatory cytokines may act as one of the signals for regulating microRNAs expression in Alzheimer's disease.
abstract: Oxidative stress and chronic inflammation are one of the earliest defects that initiate and promote Alzheimer's disease (AD). Studies showed that expressions of microRNAs were upregulated or downregulated in AD. Therefore, these biochemical defects may influence the levels of microRNAs. The up-regulated microRNAs cause neurodegeneration by: (a) decreasing the levels of a nuclear transcriptional factor-2 (Nrf2), (b) reducing the levels of α-secretase ADM10; and (c) reducing the levels of phosphatases. The down-regulated microRNAs cause neurodegeneration by: (a) increasing the levels of β-secretase, (b) increasing the levels of tau kinase; (c) elevating the levels of tau proteins; (d) increasing the levels of APP; and (e) increasing the levels of nuclear factor-kappaB (NF-kB). Antioxidants protect neurons by reducing oxidative stress and chronic inflammation. Therefore, they may also influence the levels of microRNAs. This review briefly describes the studies on changes in the expressions of microRNAs in the pathogenesis of AD. It proposes a hypothesis that free radicals and pro-inflammatory cytokines act as one of the signals that upregulate or downregulate the levels of microRNAs by influencing their transcription, processing or stability leading to neurodegeneration in AD. Antioxidants that reduce oxidative stress and pro-inflammatory cytokines also regulate the levels of microRNAs.
authors.affiliation: 245 E-Faisan Drive, San Rafael, CA 94903, USA. Electronic address: knprasad@comcast.net.
authors.forename: Kedar N
authors.initials: KN
authors.lastname: Prasad
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D035683:MicroRNAs
keywords: Antioxidants; Dementia; Inflammation; MicroRNAs; Oxidative stress