Shared Molecular Signatures Across Neurodegenerative Diseases and Herpes Virus Infections Highlights Potential Mechanisms for Maladaptive Innate Immune Responses
Growing evidence suggests that peripheral factors to the brain driving neuro-inflammation could affect Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) severity. Herpes simplex virus type 1 (HSV1) infection has been associated with AD while other related viruses, including cytomegalovirus (CMV)...
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| Veröffentlicht in: | Scientific reports 2019-06, Vol.9 (1), p.8795-16, Article 8795 |
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| description | Growing evidence suggests that peripheral factors to the brain driving neuro-inflammation could affect Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) severity. Herpes simplex virus type 1 (HSV1) infection has been associated with AD while other related viruses, including cytomegalovirus (CMV), Epstein-Bar virus and human herpesvirus 6 (HHV6), are known to infect neurons. Here we compare gene expression profiles between AD or PD patients to those afflicted with herpes viral infections as to discover novel potential neuro-inflammation pathways. We found multiple significant differentially expressed genes (DEGs) shared between AD/PD and viral infections including
SESN3
which has a genetic association for increased AD risk. Pathway enrichment analysis revealed viruses shared Oxidative Stress Defense System and LRRK2 pathways with AD and PD, respectively. We further processed our data to identify novel target and drug-repurposing opportunities including anti-inflammatory therapy, immune-modulators and cholinesterase inhibitors which could lead to new therapeutics paradigms for these neurodegenerative diseases. |
| doi_str_mv | 10.1038/s41598-019-45129-8 |
| format | Article |
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SESN3
which has a genetic association for increased AD risk. Pathway enrichment analysis revealed viruses shared Oxidative Stress Defense System and LRRK2 pathways with AD and PD, respectively. We further processed our data to identify novel target and drug-repurposing opportunities including anti-inflammatory therapy, immune-modulators and cholinesterase inhibitors which could lead to new therapeutics paradigms for these neurodegenerative diseases.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-45129-8</identifier><identifier>PMID: 31217489</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/114 ; 631/378/371 ; Alzheimer's disease ; Biomarkers - metabolism ; Cholinesterase ; Cholinesterase inhibitors ; Cytomegalovirus ; Drug Repositioning ; Gene expression ; Gene Expression Regulation ; Herpes simplex ; Herpesviridae Infections - blood ; Herpesviridae Infections - genetics ; Herpesviridae Infections - immunology ; Humanities and Social Sciences ; Humans ; Immune response ; Immunity, Innate - genetics ; Immunomodulation ; Infections ; Inflammation ; Innate immunity ; LRRK2 protein ; Microglia - metabolism ; Microglia - pathology ; Movement disorders ; multidisciplinary ; Neurodegenerative diseases ; Neurodegenerative Diseases - blood ; Neurodegenerative Diseases - genetics ; Neurodegenerative Diseases - immunology ; Neuromodulation ; Oxidative stress ; Parkinson Disease - genetics ; Parkinson's disease ; Science ; Science (multidisciplinary) ; Signal Transduction - genetics ; Viral infections ; Viruses</subject><ispartof>Scientific reports, 2019-06, Vol.9 (1), p.8795-16, Article 8795</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-e2dc81aad1d526bd86b68e3e721b4b7d944c6d11834ab79842c18b8d8254e43</citedby><cites>FETCH-LOGICAL-c474t-e2dc81aad1d526bd86b68e3e721b4b7d944c6d11834ab79842c18b8d8254e43</cites><orcidid>0000-0002-9368-627X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584587/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584587/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,41101,42170,51557,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31217489$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Costa Sa, Ana Caroline</creatorcontrib><creatorcontrib>Madsen, Heather</creatorcontrib><creatorcontrib>Brown, James R.</creatorcontrib><title>Shared Molecular Signatures Across Neurodegenerative Diseases and Herpes Virus Infections Highlights Potential Mechanisms for Maladaptive Innate Immune Responses</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Growing evidence suggests that peripheral factors to the brain driving neuro-inflammation could affect Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) severity. Herpes simplex virus type 1 (HSV1) infection has been associated with AD while other related viruses, including cytomegalovirus (CMV), Epstein-Bar virus and human herpesvirus 6 (HHV6), are known to infect neurons. Here we compare gene expression profiles between AD or PD patients to those afflicted with herpes viral infections as to discover novel potential neuro-inflammation pathways. We found multiple significant differentially expressed genes (DEGs) shared between AD/PD and viral infections including
SESN3
which has a genetic association for increased AD risk. Pathway enrichment analysis revealed viruses shared Oxidative Stress Defense System and LRRK2 pathways with AD and PD, respectively. We further processed our data to identify novel target and drug-repurposing opportunities including anti-inflammatory therapy, immune-modulators and cholinesterase inhibitors which could lead to new therapeutics paradigms for these neurodegenerative diseases.</description><subject>631/114</subject><subject>631/378/371</subject><subject>Alzheimer's disease</subject><subject>Biomarkers - metabolism</subject><subject>Cholinesterase</subject><subject>Cholinesterase inhibitors</subject><subject>Cytomegalovirus</subject><subject>Drug Repositioning</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Herpes simplex</subject><subject>Herpesviridae Infections - blood</subject><subject>Herpesviridae Infections - genetics</subject><subject>Herpesviridae Infections - immunology</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity, Innate - genetics</subject><subject>Immunomodulation</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Innate immunity</subject><subject>LRRK2 protein</subject><subject>Microglia - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Costa Sa, Ana Caroline</au><au>Madsen, Heather</au><au>Brown, James R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Shared Molecular Signatures Across Neurodegenerative Diseases and Herpes Virus Infections Highlights Potential Mechanisms for Maladaptive Innate Immune Responses</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-06-19</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>8795</spage><epage>16</epage><pages>8795-16</pages><artnum>8795</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Growing evidence suggests that peripheral factors to the brain driving neuro-inflammation could affect Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) severity. Herpes simplex virus type 1 (HSV1) infection has been associated with AD while other related viruses, including cytomegalovirus (CMV), Epstein-Bar virus and human herpesvirus 6 (HHV6), are known to infect neurons. Here we compare gene expression profiles between AD or PD patients to those afflicted with herpes viral infections as to discover novel potential neuro-inflammation pathways. We found multiple significant differentially expressed genes (DEGs) shared between AD/PD and viral infections including
SESN3
which has a genetic association for increased AD risk. Pathway enrichment analysis revealed viruses shared Oxidative Stress Defense System and LRRK2 pathways with AD and PD, respectively. We further processed our data to identify novel target and drug-repurposing opportunities including anti-inflammatory therapy, immune-modulators and cholinesterase inhibitors which could lead to new therapeutics paradigms for these neurodegenerative diseases.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31217489</pmid><doi>10.1038/s41598-019-45129-8</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-9368-627X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/114 631/378/371 Alzheimer's disease Biomarkers - metabolism Cholinesterase Cholinesterase inhibitors Cytomegalovirus Drug Repositioning Gene expression Gene Expression Regulation Herpes simplex Herpesviridae Infections - blood Herpesviridae Infections - genetics Herpesviridae Infections - immunology Humanities and Social Sciences Humans Immune response Immunity, Innate - genetics Immunomodulation Infections Inflammation Innate immunity LRRK2 protein Microglia - metabolism Microglia - pathology Movement disorders multidisciplinary Neurodegenerative diseases Neurodegenerative Diseases - blood Neurodegenerative Diseases - genetics Neurodegenerative Diseases - immunology Neuromodulation Oxidative stress Parkinson Disease - genetics Parkinson's disease Science Science (multidisciplinary) Signal Transduction - genetics Viral infections Viruses |
| title | Shared Molecular Signatures Across Neurodegenerative Diseases and Herpes Virus Infections Highlights Potential Mechanisms for Maladaptive Innate Immune Responses |
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