Inflamma-MicroRNAs in Alzheimer's Disease: From Disease Pathogenesis to Therapeutic Potentials

Abstract

Alzheimer's disease (AD) is the most common cause of senile dementia. Although AD research has made important breakthroughs, the pathogenesis of this disease remains unclear, and specific AD diagnostic biomarkers and therapeutic strategies are still lacking. Recent studies have demonstrated that neuroinflammation is involved in AD pathogenesis and is closely related to other health effects. MicroRNAs (miRNAs) are a class of endogenous short sequence non-coding RNAs that indirectly inhibit translation or directly degrade messenger RNA (mRNA) by specifically binding to its 3' untranslated region (UTR). Several broadly expressed miRNAs including miR-21, miR-146a, and miR-155, have now been shown to regulate microglia/astrocytes activation. Other miRNAs, including miR-126 and miR-132, show a progressive link to the neuroinflammatory signaling. Therefore, further studies on these inflamma-miRNAs may shed light on the pathological mechanisms of AD. The differential expression of inflamma-miRNAs (such as miR-29a, miR-125b, and miR-126-5p) in the peripheral circulation may respond to AD progression, similar to inflammation, and therefore may become potential diagnostic biomarkers for AD. Moreover, inflamma-miRNAs could also be promising therapeutic targets for AD treatment. This review provides insights into the role of inflamma-miRNAs in AD, as well as an overview of general inflamma-miRNA biology, their implications in pathophysiology, and their potential roles as biomarkers and therapeutic targets.

Keywords: diagnosis; inflammation mediators; microRNAs; pathophysiology; therapy.

FIGURE 1

Cumulative effect of inflamma-miRNAs on inflammatory signaling pathways. Multiple inflamma-miRNAs may play a synergistic role in different inflammatory pathways. For instance, miR-146a targets different components of the MyD88/TLR/NF-κB pathways and microglia polarization. MiR-155 targets SOCS1 and SHIP1, whereas miR-125b, miR-146a, miR-155, Let-7, and miR-181 regulate multiple inflammatory mediators. C/EBP transcription factors are important for various inflammatory processes such as M1/M2 polarization and are targeted by Let-7. C/EBP, CCAAT/enhancer-binding protein; DAMPs, damage-associated molecular patterns; IFR, interferon receptor; IRAK, interleukin 1 receptor-associated kinase; NF-κB, nuclear factor κB; TLRs, Toll-like receptors; TNF, tumor necrosis factor; TRAF, tumor necrosis factor receptor-associated factor.