The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis
Alzheimer's disease is the most common cause of dementia worldwide, affecting the elderly population. It is characterized by the hallmark pathology of amyloid-β deposition, neurofibrillary tangle formation, and extensive neuronal degeneration in the brain. Wealth of data related to Alzheimer�...
Gespeichert in:
| Veröffentlicht in: | PloS one 2013-11, Vol.8 (11), p.e78919-e78919 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e78919 |
|---|---|
| container_issue | 11 |
| container_start_page | e78919 |
| container_title | PloS one |
| container_volume | 8 |
| creator | Caberlotto, Laura Lauria, Mario Nguyen, Thanh-Phuong Scotti, Marco |
| description | Alzheimer's disease is the most common cause of dementia worldwide, affecting the elderly population. It is characterized by the hallmark pathology of amyloid-β deposition, neurofibrillary tangle formation, and extensive neuronal degeneration in the brain. Wealth of data related to Alzheimer's disease has been generated to date, nevertheless, the molecular mechanism underlying the etiology and pathophysiology of the disease is still unknown. Here we described a method for the combined analysis of multiple types of genome-wide data aimed at revealing convergent evidence interest that would not be captured by a standard molecular approach. Lists of Alzheimer-related genes (seed genes) were obtained from different sets of data on gene expression, SNPs, and molecular targets of drugs. Network analysis was applied for identifying the regions of the human protein-protein interaction network showing a significant enrichment in seed genes, and ultimately, in genes associated to Alzheimer's disease, due to the cumulative effect of different combinations of the starting data sets. The functional properties of these enriched modules were characterized, effectively considering the role of both Alzheimer-related seed genes and genes that closely interact with them. This approach allowed us to present evidence in favor of one of the competing theories about AD underlying processes, specifically evidence supporting a predominant role of metabolism-associated biological process terms, including autophagy, insulin and fatty acid metabolic processes in Alzheimer, with a focus on AMP-activated protein kinase. This central regulator of cellular energy homeostasis regulates a series of brain functions altered in Alzheimer's disease and could link genetic perturbation with neuronal transmission and energy regulation, representing a potential candidate to be targeted by therapy. |
| doi_str_mv | 10.1371/journal.pone.0078919 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1450256504</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A478300826</galeid><doaj_id>oai_doaj_org_article_e7de5acdd95b4b69b2ef299f6f5749ee</doaj_id><sourcerecordid>A478300826</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-513a75a39c05e66a232bb03d7f2d3df4195cb1c88eb1c119938a7579fd5a55853</originalsourceid><addsrcrecordid>eNqNk11v0zAUhiMEYmPwDxBYmsTHRYs_4iTmAqma-Kg0NASDW8tJThpvjl3shFF-Pe6aTQ3aBbJkW_bzvj4-9kmSpwTPCcvJmws3eKvMfO0szDHOC0HEveSQCEZnGcXs_t78IHkUwgXGnBVZ9jA5oCnNeE6Lw-TqvAVUge29Msg7A8g1aPH5y-xSWxUAKVsjsOBXG9S6DlzoVdAB6W6ttO-iDmmLFuZPC7oD_zKgWgeIwrdIoW4wvW5U1TuPLPRXzl9GP2U20eFx8qBRJsCTcTxKvn94f37yaXZ69nF5sjidVTkv-hknTOVcMVFhDlmmKKNliVmdN7RmdZMSwauSVEUBsSdECFZEPhdNzRXnBWdHyfOd79q4IMecBUlSjinPOE4jsdwRtVMXcu11p_xGOqXl9YLzK6l8rysDEvIauKrqWvAyLTNRUmioEE3W8DwVANHr3XjaUHZQj3mdmE53rG7lyv2SrKA5LrbBvBoNvPs5QOhlp0MFxigLbtjGnRHGcnYd9_E_6N23G6mVihfQtnHx3GprKhdpXjCMC5pFan4HFVsNna7iB2t0XJ8IXk8Ekenhd79SQwhy-e3r_7NnP6bsiz22BWX6Njgz9NrZMAXTHVh5F4KH5jbJBMttfdxkQ27rQ471EWXP9h_oVnRTEOwvjIkL3w</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1450256504</pqid></control><display><type>article</type><title>The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Public Library of Science (PLoS)</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Caberlotto, Laura ; Lauria, Mario ; Nguyen, Thanh-Phuong ; Scotti, Marco</creator><contributor>Csermely, Peter</contributor><creatorcontrib>Caberlotto, Laura ; Lauria, Mario ; Nguyen, Thanh-Phuong ; Scotti, Marco ; Csermely, Peter</creatorcontrib><description>Alzheimer's disease is the most common cause of dementia worldwide, affecting the elderly population. It is characterized by the hallmark pathology of amyloid-β deposition, neurofibrillary tangle formation, and extensive neuronal degeneration in the brain. Wealth of data related to Alzheimer's disease has been generated to date, nevertheless, the molecular mechanism underlying the etiology and pathophysiology of the disease is still unknown. Here we described a method for the combined analysis of multiple types of genome-wide data aimed at revealing convergent evidence interest that would not be captured by a standard molecular approach. Lists of Alzheimer-related genes (seed genes) were obtained from different sets of data on gene expression, SNPs, and molecular targets of drugs. Network analysis was applied for identifying the regions of the human protein-protein interaction network showing a significant enrichment in seed genes, and ultimately, in genes associated to Alzheimer's disease, due to the cumulative effect of different combinations of the starting data sets. The functional properties of these enriched modules were characterized, effectively considering the role of both Alzheimer-related seed genes and genes that closely interact with them. This approach allowed us to present evidence in favor of one of the competing theories about AD underlying processes, specifically evidence supporting a predominant role of metabolism-associated biological process terms, including autophagy, insulin and fatty acid metabolic processes in Alzheimer, with a focus on AMP-activated protein kinase. This central regulator of cellular energy homeostasis regulates a series of brain functions altered in Alzheimer's disease and could link genetic perturbation with neuronal transmission and energy regulation, representing a potential candidate to be targeted by therapy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0078919</identifier><identifier>PMID: 24265728</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alzheimer Disease - genetics ; Alzheimer Disease - metabolism ; Alzheimer's disease ; AMP ; AMP-activated protein kinase ; AMP-Activated Protein Kinases - metabolism ; Amyloid ; Anopheles ; Autophagy ; Biological activity ; Biology ; Brain ; Brain research ; Cluster Analysis ; Datasets ; Degeneration ; Dementia disorders ; Development and progression ; Disease susceptibility ; Energy balance ; Energy Metabolism ; Energy transmission ; Etiology ; Fatty acids ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Genes ; Genomes ; Genomics ; Geriatrics ; Homeostasis ; Humans ; Insulin ; Kinases ; Metabolism ; Methods ; Molecular Sequence Annotation ; Network analysis ; Neurodegeneration ; Neurosciences ; Older people ; Phagocytosis ; Phosphorylation ; Physiological aspects ; Protein interaction ; Protein Interaction Mapping ; Protein Interaction Maps ; Protein kinases ; Protein-protein interactions ; Proteins ; R&D ; Research & development ; Signal Transduction ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e78919-e78919</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Caberlotto et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Caberlotto et al 2013 Caberlotto et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-513a75a39c05e66a232bb03d7f2d3df4195cb1c88eb1c119938a7579fd5a55853</citedby><cites>FETCH-LOGICAL-c758t-513a75a39c05e66a232bb03d7f2d3df4195cb1c88eb1c119938a7579fd5a55853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827084/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827084/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24265728$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Csermely, Peter</contributor><creatorcontrib>Caberlotto, Laura</creatorcontrib><creatorcontrib>Lauria, Mario</creatorcontrib><creatorcontrib>Nguyen, Thanh-Phuong</creatorcontrib><creatorcontrib>Scotti, Marco</creatorcontrib><title>The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Alzheimer's disease is the most common cause of dementia worldwide, affecting the elderly population. It is characterized by the hallmark pathology of amyloid-β deposition, neurofibrillary tangle formation, and extensive neuronal degeneration in the brain. Wealth of data related to Alzheimer's disease has been generated to date, nevertheless, the molecular mechanism underlying the etiology and pathophysiology of the disease is still unknown. Here we described a method for the combined analysis of multiple types of genome-wide data aimed at revealing convergent evidence interest that would not be captured by a standard molecular approach. Lists of Alzheimer-related genes (seed genes) were obtained from different sets of data on gene expression, SNPs, and molecular targets of drugs. Network analysis was applied for identifying the regions of the human protein-protein interaction network showing a significant enrichment in seed genes, and ultimately, in genes associated to Alzheimer's disease, due to the cumulative effect of different combinations of the starting data sets. The functional properties of these enriched modules were characterized, effectively considering the role of both Alzheimer-related seed genes and genes that closely interact with them. This approach allowed us to present evidence in favor of one of the competing theories about AD underlying processes, specifically evidence supporting a predominant role of metabolism-associated biological process terms, including autophagy, insulin and fatty acid metabolic processes in Alzheimer, with a focus on AMP-activated protein kinase. This central regulator of cellular energy homeostasis regulates a series of brain functions altered in Alzheimer's disease and could link genetic perturbation with neuronal transmission and energy regulation, representing a potential candidate to be targeted by therapy.</description><subject>Alzheimer Disease - genetics</subject><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>AMP</subject><subject>AMP-activated protein kinase</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Amyloid</subject><subject>Anopheles</subject><subject>Autophagy</subject><subject>Biological activity</subject><subject>Biology</subject><subject>Brain</subject><subject>Brain research</subject><subject>Cluster Analysis</subject><subject>Datasets</subject><subject>Degeneration</subject><subject>Dementia disorders</subject><subject>Development and progression</subject><subject>Disease susceptibility</subject><subject>Energy balance</subject><subject>Energy Metabolism</subject><subject>Energy transmission</subject><subject>Etiology</subject><subject>Fatty acids</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Gene Regulatory Networks</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Geriatrics</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Insulin</subject><subject>Kinases</subject><subject>Metabolism</subject><subject>Methods</subject><subject>Molecular Sequence Annotation</subject><subject>Network analysis</subject><subject>Neurodegeneration</subject><subject>Neurosciences</subject><subject>Older people</subject><subject>Phagocytosis</subject><subject>Phosphorylation</subject><subject>Physiological aspects</subject><subject>Protein interaction</subject><subject>Protein Interaction Mapping</subject><subject>Protein Interaction Maps</subject><subject>Protein kinases</subject><subject>Protein-protein interactions</subject><subject>Proteins</subject><subject>R&D</subject><subject>Research & development</subject><subject>Signal Transduction</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11v0zAUhiMEYmPwDxBYmsTHRYs_4iTmAqma-Kg0NASDW8tJThpvjl3shFF-Pe6aTQ3aBbJkW_bzvj4-9kmSpwTPCcvJmws3eKvMfO0szDHOC0HEveSQCEZnGcXs_t78IHkUwgXGnBVZ9jA5oCnNeE6Lw-TqvAVUge29Msg7A8g1aPH5y-xSWxUAKVsjsOBXG9S6DlzoVdAB6W6ttO-iDmmLFuZPC7oD_zKgWgeIwrdIoW4wvW5U1TuPLPRXzl9GP2U20eFx8qBRJsCTcTxKvn94f37yaXZ69nF5sjidVTkv-hknTOVcMVFhDlmmKKNliVmdN7RmdZMSwauSVEUBsSdECFZEPhdNzRXnBWdHyfOd79q4IMecBUlSjinPOE4jsdwRtVMXcu11p_xGOqXl9YLzK6l8rysDEvIauKrqWvAyLTNRUmioEE3W8DwVANHr3XjaUHZQj3mdmE53rG7lyv2SrKA5LrbBvBoNvPs5QOhlp0MFxigLbtjGnRHGcnYd9_E_6N23G6mVihfQtnHx3GprKhdpXjCMC5pFan4HFVsNna7iB2t0XJ8IXk8Ekenhd79SQwhy-e3r_7NnP6bsiz22BWX6Njgz9NrZMAXTHVh5F4KH5jbJBMttfdxkQ27rQ471EWXP9h_oVnRTEOwvjIkL3w</recordid><startdate>20131112</startdate><enddate>20131112</enddate><creator>Caberlotto, Laura</creator><creator>Lauria, Mario</creator><creator>Nguyen, Thanh-Phuong</creator><creator>Scotti, Marco</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20131112</creationdate><title>The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis</title><author>Caberlotto, Laura ; Lauria, Mario ; Nguyen, Thanh-Phuong ; Scotti, Marco</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-513a75a39c05e66a232bb03d7f2d3df4195cb1c88eb1c119938a7579fd5a55853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Alzheimer Disease - genetics</topic><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>AMP</topic><topic>AMP-activated protein kinase</topic><topic>AMP-Activated Protein Kinases - metabolism</topic><topic>Amyloid</topic><topic>Anopheles</topic><topic>Autophagy</topic><topic>Biological activity</topic><topic>Biology</topic><topic>Brain</topic><topic>Brain research</topic><topic>Cluster Analysis</topic><topic>Datasets</topic><topic>Degeneration</topic><topic>Dementia disorders</topic><topic>Development and progression</topic><topic>Disease susceptibility</topic><topic>Energy balance</topic><topic>Energy Metabolism</topic><topic>Energy transmission</topic><topic>Etiology</topic><topic>Fatty acids</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Gene Regulatory Networks</topic><topic>Genes</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Geriatrics</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Insulin</topic><topic>Kinases</topic><topic>Metabolism</topic><topic>Methods</topic><topic>Molecular Sequence Annotation</topic><topic>Network analysis</topic><topic>Neurodegeneration</topic><topic>Neurosciences</topic><topic>Older people</topic><topic>Phagocytosis</topic><topic>Phosphorylation</topic><topic>Physiological aspects</topic><topic>Protein interaction</topic><topic>Protein Interaction Mapping</topic><topic>Protein Interaction Maps</topic><topic>Protein kinases</topic><topic>Protein-protein interactions</topic><topic>Proteins</topic><topic>R&D</topic><topic>Research & development</topic><topic>Signal Transduction</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caberlotto, Laura</creatorcontrib><creatorcontrib>Lauria, Mario</creatorcontrib><creatorcontrib>Nguyen, Thanh-Phuong</creatorcontrib><creatorcontrib>Scotti, Marco</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caberlotto, Laura</au><au>Lauria, Mario</au><au>Nguyen, Thanh-Phuong</au><au>Scotti, Marco</au><au>Csermely, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-12</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e78919</spage><epage>e78919</epage><pages>e78919-e78919</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Alzheimer's disease is the most common cause of dementia worldwide, affecting the elderly population. It is characterized by the hallmark pathology of amyloid-β deposition, neurofibrillary tangle formation, and extensive neuronal degeneration in the brain. Wealth of data related to Alzheimer's disease has been generated to date, nevertheless, the molecular mechanism underlying the etiology and pathophysiology of the disease is still unknown. Here we described a method for the combined analysis of multiple types of genome-wide data aimed at revealing convergent evidence interest that would not be captured by a standard molecular approach. Lists of Alzheimer-related genes (seed genes) were obtained from different sets of data on gene expression, SNPs, and molecular targets of drugs. Network analysis was applied for identifying the regions of the human protein-protein interaction network showing a significant enrichment in seed genes, and ultimately, in genes associated to Alzheimer's disease, due to the cumulative effect of different combinations of the starting data sets. The functional properties of these enriched modules were characterized, effectively considering the role of both Alzheimer-related seed genes and genes that closely interact with them. This approach allowed us to present evidence in favor of one of the competing theories about AD underlying processes, specifically evidence supporting a predominant role of metabolism-associated biological process terms, including autophagy, insulin and fatty acid metabolic processes in Alzheimer, with a focus on AMP-activated protein kinase. This central regulator of cellular energy homeostasis regulates a series of brain functions altered in Alzheimer's disease and could link genetic perturbation with neuronal transmission and energy regulation, representing a potential candidate to be targeted by therapy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24265728</pmid><doi>10.1371/journal.pone.0078919</doi><tpages>e78919</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-11, Vol.8 (11), p.e78919-e78919 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1450256504 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Alzheimer Disease - genetics Alzheimer Disease - metabolism Alzheimer's disease AMP AMP-activated protein kinase AMP-Activated Protein Kinases - metabolism Amyloid Anopheles Autophagy Biological activity Biology Brain Brain research Cluster Analysis Datasets Degeneration Dementia disorders Development and progression Disease susceptibility Energy balance Energy Metabolism Energy transmission Etiology Fatty acids Gene expression Gene Expression Profiling Gene Expression Regulation Gene Regulatory Networks Genes Genomes Genomics Geriatrics Homeostasis Humans Insulin Kinases Metabolism Methods Molecular Sequence Annotation Network analysis Neurodegeneration Neurosciences Older people Phagocytosis Phosphorylation Physiological aspects Protein interaction Protein Interaction Mapping Protein Interaction Maps Protein kinases Protein-protein interactions Proteins R&D Research & development Signal Transduction Single nucleotide polymorphisms Single-nucleotide polymorphism |
| title | The central role of AMP-kinase and energy homeostasis impairment in Alzheimer's disease: a multifactor network analysis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T12%3A01%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20central%20role%20of%20AMP-kinase%20and%20energy%20homeostasis%20impairment%20in%20Alzheimer's%20disease:%20a%20multifactor%20network%20analysis&rft.jtitle=PloS%20one&rft.au=Caberlotto,%20Laura&rft.date=2013-11-12&rft.volume=8&rft.issue=11&rft.spage=e78919&rft.epage=e78919&rft.pages=e78919-e78919&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0078919&rft_dat=%3Cgale_plos_%3EA478300826%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1450256504&rft_id=info:pmid/24265728&rft_galeid=A478300826&rft_doaj_id=oai_doaj_org_article_e7de5acdd95b4b69b2ef299f6f5749ee&rfr_iscdi=true |