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Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat

Despite major strides in personalized genomics, it remains poorly understood why neurodegenerative diseases occur in only a fraction of individuals with a genetic predisposition and conversely, why individuals with no genetic risk of a disorder develop one. Chronic diseases like Alzheimer's, Pa...

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Autores principales: Patrick, Kristin L., Bell, Samantha L., Weindel, Chi G., Watson, Robert O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546885/
https://www.ncbi.nlm.nih.gov/pubmed/31192157
http://dx.doi.org/10.3389/fcimb.2019.00138
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author Patrick, Kristin L.
Bell, Samantha L.
Weindel, Chi G.
Watson, Robert O.
author_facet Patrick, Kristin L.
Bell, Samantha L.
Weindel, Chi G.
Watson, Robert O.
author_sort Patrick, Kristin L.
collection PubMed
description Despite major strides in personalized genomics, it remains poorly understood why neurodegenerative diseases occur in only a fraction of individuals with a genetic predisposition and conversely, why individuals with no genetic risk of a disorder develop one. Chronic diseases like Alzheimer's, Parkinson's, and Multiple sclerosis are speculated to result from a combination of genetic and environmental factors, a concept commonly referred to as the “multiple hit hypothesis.” A number of bacterial infections have been linked to increased risk of neurodegeneration, and in some cases, clearance of bacterial pathogens has been correlated with amelioration of central nervous system (CNS) deficits. Additionally, mutations in several genes known to contribute to CNS disorders like Parkinson's Disease have repeatedly been implicated in susceptibility to intracellular bacterial infection. Recent data has begun to demonstrate roles for these genes (PARK2, PINK1, and LRRK2) in modulating innate immune outcomes, suggesting that immune dysregulation may play an even more important role in neurodegeneration than previously appreciated. This review will broadly explore the connections between bacterial infection, immune dysregulation, and CNS disorders. Understanding this interplay and how bacterial pathogenesis contributes to the “multiple-hit hypothesis” of neurodegeneration will be crucial to develop therapeutics to effectively treat both neurodegeneration and infection.
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spelling pubmed-65468852019-06-12 Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat Patrick, Kristin L. Bell, Samantha L. Weindel, Chi G. Watson, Robert O. Front Cell Infect Microbiol Cellular and Infection Microbiology Despite major strides in personalized genomics, it remains poorly understood why neurodegenerative diseases occur in only a fraction of individuals with a genetic predisposition and conversely, why individuals with no genetic risk of a disorder develop one. Chronic diseases like Alzheimer's, Parkinson's, and Multiple sclerosis are speculated to result from a combination of genetic and environmental factors, a concept commonly referred to as the “multiple hit hypothesis.” A number of bacterial infections have been linked to increased risk of neurodegeneration, and in some cases, clearance of bacterial pathogens has been correlated with amelioration of central nervous system (CNS) deficits. Additionally, mutations in several genes known to contribute to CNS disorders like Parkinson's Disease have repeatedly been implicated in susceptibility to intracellular bacterial infection. Recent data has begun to demonstrate roles for these genes (PARK2, PINK1, and LRRK2) in modulating innate immune outcomes, suggesting that immune dysregulation may play an even more important role in neurodegeneration than previously appreciated. This review will broadly explore the connections between bacterial infection, immune dysregulation, and CNS disorders. Understanding this interplay and how bacterial pathogenesis contributes to the “multiple-hit hypothesis” of neurodegeneration will be crucial to develop therapeutics to effectively treat both neurodegeneration and infection. Frontiers Media S.A. 2019-05-28 /pmc/articles/PMC6546885/ /pubmed/31192157 http://dx.doi.org/10.3389/fcimb.2019.00138 Text en Copyright © 2019 Patrick, Bell, Weindel and Watson. 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(s) 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 Cellular and Infection Microbiology
Patrick, Kristin L.
Bell, Samantha L.
Weindel, Chi G.
Watson, Robert O.
Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat
title Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat
title_full Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat
title_fullStr Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat
title_full_unstemmed Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat
title_short Exploring the “Multiple-Hit Hypothesis” of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat
title_sort exploring the “multiple-hit hypothesis” of neurodegenerative disease: bacterial infection comes up to bat
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546885/
https://www.ncbi.nlm.nih.gov/pubmed/31192157
http://dx.doi.org/10.3389/fcimb.2019.00138
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