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Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease
The first indication of a potential mechanistic link between the pathobiology of the human gastrointestinal (GI)-tract microbiome and its contribution to the pathogenetic mechanisms of sporadic Alzheimer’s disease (AD) came a scant 4 years ago (1). Ongoing research continues to strengthen the hypoth...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867462/ https://www.ncbi.nlm.nih.gov/pubmed/29615954 http://dx.doi.org/10.3389/fneur.2018.00145 |
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author | Zhao, Yuhai Lukiw, Walter J. |
author_facet | Zhao, Yuhai Lukiw, Walter J. |
author_sort | Zhao, Yuhai |
collection | PubMed |
description | The first indication of a potential mechanistic link between the pathobiology of the human gastrointestinal (GI)-tract microbiome and its contribution to the pathogenetic mechanisms of sporadic Alzheimer’s disease (AD) came a scant 4 years ago (1). Ongoing research continues to strengthen the hypothesis that neurotoxic microbial-derived components of the GI tract microbiome can cross aging GI tract and blood–brain barriers and contribute to progressive proinflammatory neurodegeneration, as exemplified by the AD-process. Of central interest in these recent investigations are the pathological roles played by human GI tract resident Gram-negative anaerobic bacteria and neurotropic viruses—two prominent divisions of GI tract microbiome-derived microbiota—which harbor considerable pathogenic potential. It is noteworthy that the first two well-studied microbiota—the GI tract abundant Gram-negative bacteria Bacteroides fragilis and the neurotropic herpes simplex virus-1 both share a final common pathway of NF-κB (p50/p65) activation and microRNA-146a induction with ensuing pathogenic stimulation of innate-immune and neuroinflammatory pathways. These appear to strongly contribute to the inflammation-mediated amyloidogenic neuropathology of AD. This communication: (i) will review recent research contributions that have expanded our understanding of the nature of the translocation of microbiome-derived neurotoxins-across biophysiological barriers; (ii) will assess multiple-recent investigations of the induction of the proinflammatory pathogenic microRNA-146a by these two prominent classes of human microbiota; and (iii) will discuss the role of molecular neurobiology and mechanistic contribution of polymicrobial infections to AD-type neuropathological change. |
format | Online Article Text |
id | pubmed-5867462 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-58674622018-04-03 Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease Zhao, Yuhai Lukiw, Walter J. Front Neurol Neuroscience The first indication of a potential mechanistic link between the pathobiology of the human gastrointestinal (GI)-tract microbiome and its contribution to the pathogenetic mechanisms of sporadic Alzheimer’s disease (AD) came a scant 4 years ago (1). Ongoing research continues to strengthen the hypothesis that neurotoxic microbial-derived components of the GI tract microbiome can cross aging GI tract and blood–brain barriers and contribute to progressive proinflammatory neurodegeneration, as exemplified by the AD-process. Of central interest in these recent investigations are the pathological roles played by human GI tract resident Gram-negative anaerobic bacteria and neurotropic viruses—two prominent divisions of GI tract microbiome-derived microbiota—which harbor considerable pathogenic potential. It is noteworthy that the first two well-studied microbiota—the GI tract abundant Gram-negative bacteria Bacteroides fragilis and the neurotropic herpes simplex virus-1 both share a final common pathway of NF-κB (p50/p65) activation and microRNA-146a induction with ensuing pathogenic stimulation of innate-immune and neuroinflammatory pathways. These appear to strongly contribute to the inflammation-mediated amyloidogenic neuropathology of AD. This communication: (i) will review recent research contributions that have expanded our understanding of the nature of the translocation of microbiome-derived neurotoxins-across biophysiological barriers; (ii) will assess multiple-recent investigations of the induction of the proinflammatory pathogenic microRNA-146a by these two prominent classes of human microbiota; and (iii) will discuss the role of molecular neurobiology and mechanistic contribution of polymicrobial infections to AD-type neuropathological change. Frontiers Media S.A. 2018-03-19 /pmc/articles/PMC5867462/ /pubmed/29615954 http://dx.doi.org/10.3389/fneur.2018.00145 Text en Copyright © 2018 Zhao and Lukiw. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Zhao, Yuhai Lukiw, Walter J. Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease |
title | Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease |
title_full | Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease |
title_fullStr | Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease |
title_full_unstemmed | Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease |
title_short | Microbiome-Mediated Upregulation of MicroRNA-146a in Sporadic Alzheimer’s Disease |
title_sort | microbiome-mediated upregulation of microrna-146a in sporadic alzheimer’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5867462/ https://www.ncbi.nlm.nih.gov/pubmed/29615954 http://dx.doi.org/10.3389/fneur.2018.00145 |
work_keys_str_mv | AT zhaoyuhai microbiomemediatedupregulationofmicrorna146ainsporadicalzheimersdisease AT lukiwwalterj microbiomemediatedupregulationofmicrorna146ainsporadicalzheimersdisease |