{"corpus_id":13814751,"paper_sha":"2c6f863e6a8bf13884d5741bd16682af9a59b7c4","doi":"10.1186/s40478-016-0286-7","arxiv_id":null,"pmid":26891847,"pmcid":"4758105","mag_id":2281234882,"dblp_id":null,"acl_id":null,"title":"Neuregulin 1 confers neuroprotection in SOD1-linked amyotrophic lateral sclerosis mice via restoration of C-boutons of spinal motor neurons","year":2016,"publication_date":"2016-02-18","venue":"Acta Neuropathologica Communications","journal":{"name":"Acta Neuropathologica Communications","pages":null,"volume":"4"},"journal_issn":null,"journal_title":null,"publication_types":["JournalArticle"],"pubmed_pub_types":["Journal Article","Research Support, Non-U.S. Gov't"],"s2_fields_of_study":["Biology","Medicine"],"reference_count":34,"citation_count":52,"influential_citation_count":1,"is_open_access":true,"arxiv_categories":null,"arxiv_license":null,"arxiv_journal_ref":null,"mesh_headings":[{"d":"Adult","mj":false,"ui":"D000328"},{"d":"Age Factors","mj":false,"ui":"D000367"},{"d":"Aged","mj":false,"ui":"D000368"},{"d":"Aged, 80 and over","mj":false,"ui":"D000369"},{"d":"Amyotrophic Lateral Sclerosis","mj":true,"qs":[{"q":"drug therapy","mj":false,"ui":"Q000188"},{"q":"genetics","mj":false,"ui":"Q000235"},{"q":"pathology","mj":false,"ui":"Q000473"}],"ui":"D000690"},{"d":"Animals","mj":false,"ui":"D000818"},{"d":"Disease Models, Animal","mj":false,"ui":"D004195"},{"d":"Female","mj":false,"ui":"D005260"},{"d":"Gene Expression Regulation","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D005786"},{"d":"Humans","mj":false,"ui":"D006801"},{"d":"Male","mj":false,"ui":"D008297"},{"d":"Membrane Proteins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D008565"},{"d":"Mice","mj":false,"ui":"D051379"},{"d":"Mice, Inbred C57BL","mj":false,"ui":"D008810"},{"d":"Mice, Transgenic","mj":false,"ui":"D008822"},{"d":"Middle Aged","mj":false,"ui":"D008875"},{"d":"Motor Neurons","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"},{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D009046"},{"d":"Mutation","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D009154"},{"d":"Nerve Tissue Proteins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D009419"},{"d":"Neuregulin-1","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D020890"},{"d":"Neuroprotection","mj":false,"qs":[{"q":"physiology","mj":true,"ui":"Q000502"}],"ui":"D000066829"},{"d":"Postmortem Changes","mj":false,"ui":"D011180"},{"d":"Presynaptic Terminals","mj":false,"qs":[{"q":"metabolism","mj":true,"ui":"Q000378"}],"ui":"D017729"},{"d":"Receptor, ErbB-3","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D020893"},{"d":"Shab Potassium Channels","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D051669"},{"d":"Spinal Cord","mj":false,"qs":[{"q":"pathology","mj":true,"ui":"Q000473"}],"ui":"D013116"},{"d":"Superoxide Dismutase","mj":false,"qs":[{"q":"genetics","mj":false,"ui":"Q000235"}],"ui":"D013482"},{"d":"Superoxide Dismutase-1","mj":false,"ui":"D000072105"},{"d":"Vesicular Acetylcholine Transport Proteins","mj":false,"qs":[{"q":"metabolism","mj":false,"ui":"Q000378"}],"ui":"D050494"}],"chemicals":[{"n":"Membrane Proteins","ui":"D008565","reg":"0"},{"n":"Nerve Tissue Proteins","ui":"D009419","reg":"0"},{"n":"Neuregulin-1","ui":"D020890","reg":"0"},{"n":"SOD1 protein, human","ui":"C000606290","reg":"0"},{"n":"Shab Potassium Channels","ui":"D051669","reg":"0"},{"n":"Slc18a3 protein, mouse","ui":"C493460","reg":"0"},{"n":"Vesicular Acetylcholine Transport Proteins","ui":"D050494","reg":"0"},{"n":"Sod1 protein, mouse","ui":"C000606291","reg":"EC 1.15.1.1"},{"n":"Superoxide Dismutase","ui":"D013482","reg":"EC 1.15.1.1"},{"n":"Superoxide Dismutase-1","ui":"D000072105","reg":"EC 1.15.1.1"},{"n":"ERBB3 protein, human","ui":"C581292","reg":"EC 2.7.10.1"},{"n":"Receptor, ErbB-3","ui":"D020893","reg":"EC 2.7.10.1"}],"comments_corrections":null,"source_flags":5,"s2_open_access_pdf_url":"https://actaneurocomms.biomedcentral.com/track/pdf/10.1186/s40478-016-0286-7","s2_open_access_landing_url":"https://www.semanticscholar.org/paper/6e155f4cb61618110fa97c907096160ab3190eab","s2_open_access_license":"CCBY","s2_open_access_status":"GOLD","pmc_open_access_pdf_url":null,"pmc_open_access_landing_url":null,"pmc_open_access_license":null,"pmc_open_access_status":null,"unpaywall_open_access_pdf_url":null,"unpaywall_open_access_landing_url":null,"unpaywall_open_access_license":null,"unpaywall_open_access_status":null,"abstract":"IntroductionIncreasing evidence implicates the role of the cell types surrounding motor neurons, such as interneurons and glial cells, in non-cell autonomous neurodegeneration of amyotrophic lateral sclerosis (ALS). C-boutons, the large cholinergic synapses that innervate spinal α-motor neurons to control their excitability, are progressively lost from motor neurons in both human ALS and mutant Cu/Zn superoxide dismutase 1 (SOD1)-ALS mice. Neuregulin-1 (NRG1), a trophic factor implicated in neural development, transmission, and synaptic plasticity, has been reported to localize in the synapse of C-boutons. However, the roles of NRG1 in maintenance of motor neuron health and activity, as well as the functional consequences of its alteration in motor neuron disease, are not fully understood.ResultsNRG1 was localized to the post-synaptic face of C-boutons and its expression was significantly lost in SOD1-ALS mice and human ALS patients. Losses of NRG1 expression and C-boutons occured almost contemporaneously in SOD1-ALS mice. In addition, expressions of ErbB3 and ErbB4, receptors for NRG1, were reduced in the motor neurons of SOD1-ALS mice. Furthermore, viral-mediated delivery of type III-NRG1 to the spinal cord restored the number of C-boutons and extended the survival time of SOD1-ALS mice.ConclusionsThese results suggest that maintenance of NRG1-ErbB4/3 axis by supplementation of NRG1 confers neuroprotection in motor neuron disease, partly through the maintenance of C-boutons of spinal motor neurons.","claims":[{"public_id":"cl_ef2bb6b881eb53a2bdff09c5d9450fa6","status":"active","text":"ErbB3 and ErbB4 expression is reduced in motor neurons of SOD1-ALS mice.","confidence":0.95,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_ef2bb6b881eb53a2bdff09c5d9450fa6"},{"public_id":"cl_b56cc968acd64f89864237916b75a9b2","status":"active","text":"Loss of NRG1 expression occurs almost contemporaneously with loss of C-boutons in SOD1-ALS 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neurons.","confidence":0.92,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_5f7c6a1c8908b57ec5d9015018cc6f29"},{"public_id":"cl_3d1fd3f4e725bbfefaf3dcbe3c89ebc0","status":"active","text":"Viral-mediated delivery of type III-NRG1 to the spinal cord restores C-bouton number and extends survival in SOD1-ALS mice.","confidence":0.98,"contributors":[{"id":1,"public_id":"12632b8b5f","public_label":"Anonymous (12632b8b5f)","roles":["extraction"],"url":"https://sah.borca.ai/u/12632b8b5f"}],"url":"https://sah.borca.ai/claims/cl_3d1fd3f4e725bbfefaf3dcbe3c89ebc0"}],"concepts":[{"public_id":"co_0d23b704841d8207b06fc770e3fa6e41","status":"active","name":"motor neuron disease","description":"A group of disorders characterized by degeneration of motor neurons.","types":["disease 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