Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons
Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-termi...
Gespeichert in:
| Veröffentlicht in: | The Journal of biological chemistry 2011-01, Vol.286 (4), p.2675-2680 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2680 |
|---|---|
| container_issue | 4 |
| container_start_page | 2675 |
| container_title | The Journal of biological chemistry |
| container_volume | 286 |
| creator | Hellman, Maarit Arumäe, Urmas Yu, Li-ying Lindholm, Päivi Peränen, Johan Saarma, Mart Permi, Perttu |
| description | Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well known inhibitor of proapoptotic Bax (Bcl-2-associated X protein). Cellular studies confirm that MANF and C-MANF protect neurons intracellularly as efficiently as Ku70. |
| doi_str_mv | 10.1074/jbc.M110.146738 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3024763</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0021925820541409</els_id><sourcerecordid>872125657</sourcerecordid><originalsourceid>FETCH-LOGICAL-c530t-d350eb2116b2869b66c880c70f3fb3d0b21cf10177feb79bbf2c7cf564366ffa3</originalsourceid><addsrcrecordid>eNqFkUFv1DAQhS0EokvhzA1yAw5px3ZiJxekVcVSpG6RgJW4WY4z7rrKxsH2rtR_j5eUCg4IXyzP--bZ40fISwpnFGR1ftuZszU9niohefOILCg0vOQ1_f6YLAAYLVtWNyfkWYy3kFfV0qfkhFGopGxgQXZrjDganLZ6cKZYxhS8uUtY9hjcAfviGvfB5-K0zfJKm-RD8Xa9vF69Ky51LHSxGd2PPRZrNFs9urgrki--YDS5tpz8lHzKjb9cxvicPLF6iPjifj8lm9WHbxeX5dXnj58ullelqTmksuc1YMcoFR1rRNsJYZoGjATLbcd7yJKxFKiUFjvZdp1lRhpbi4oLYa3mp-T97Dvtux32BscU9KCm4HY63CmvnfpbGd1W3fiD4sAqKXg2eHNvEHyeLia1c9HgMOgR_T6qFiStQTL6X7LJEKtFLTN5PpMm-BgD2of3UFDHNFVOUx3TVHOauePVn2M88L_jy8DrGbDaK30TXFSbrwwoB9ryChqRiXYmMH_3wWFQ0bhj4L0LaJLqvfvn9T8BjY25IA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>872125657</pqid></control><display><type>article</type><title>Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Hellman, Maarit ; Arumäe, Urmas ; Yu, Li-ying ; Lindholm, Päivi ; Peränen, Johan ; Saarma, Mart ; Permi, Perttu</creator><creatorcontrib>Hellman, Maarit ; Arumäe, Urmas ; Yu, Li-ying ; Lindholm, Päivi ; Peränen, Johan ; Saarma, Mart ; Permi, Perttu</creatorcontrib><description>Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well known inhibitor of proapoptotic Bax (Bcl-2-associated X protein). Cellular studies confirm that MANF and C-MANF protect neurons intracellularly as efficiently as Ku70.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.M110.146738</identifier><identifier>PMID: 21047780</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antigens, Nuclear - genetics ; Antigens, Nuclear - metabolism ; Apoptosis ; Bax ; bcl-2-Associated X Protein - genetics ; bcl-2-Associated X Protein - metabolism ; Cells, Cultured ; Disease Models, Animal ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; Humans ; Ku Autoantigen ; Ku70 ; Nerve Growth Factors - genetics ; Nerve Growth Factors - metabolism ; Neurodegeneration ; Neurons - metabolism ; Neurotrophic Factor ; NMR ; Nuclear Magnetic Resonance, Biomolecular ; Oxidopamine - adverse effects ; Oxidopamine - pharmacology ; Parkinson Disease ; Parkinson Disease, Secondary - chemically induced ; Parkinson Disease, Secondary - genetics ; Parkinson Disease, Secondary - metabolism ; Protein Structure and Folding ; Protein Structure, Tertiary ; Proteins - genetics ; Proteins - metabolism ; Rats ; Structural Homology, Protein ; Sympatholytics - adverse effects ; Sympatholytics - pharmacokinetics</subject><ispartof>The Journal of biological chemistry, 2011-01, Vol.286 (4), p.2675-2680</ispartof><rights>2011 © 2011 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.</rights><rights>2011 by The American Society for Biochemistry and Molecular Biology, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c530t-d350eb2116b2869b66c880c70f3fb3d0b21cf10177feb79bbf2c7cf564366ffa3</citedby><cites>FETCH-LOGICAL-c530t-d350eb2116b2869b66c880c70f3fb3d0b21cf10177feb79bbf2c7cf564366ffa3</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/PMC3024763/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024763/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21047780$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hellman, Maarit</creatorcontrib><creatorcontrib>Arumäe, Urmas</creatorcontrib><creatorcontrib>Yu, Li-ying</creatorcontrib><creatorcontrib>Lindholm, Päivi</creatorcontrib><creatorcontrib>Peränen, Johan</creatorcontrib><creatorcontrib>Saarma, Mart</creatorcontrib><creatorcontrib>Permi, Perttu</creatorcontrib><title>Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well known inhibitor of proapoptotic Bax (Bcl-2-associated X protein). Cellular studies confirm that MANF and C-MANF protect neurons intracellularly as efficiently as Ku70.</description><subject>Animals</subject><subject>Antigens, Nuclear - genetics</subject><subject>Antigens, Nuclear - metabolism</subject><subject>Apoptosis</subject><subject>Bax</subject><subject>bcl-2-Associated X Protein - genetics</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Humans</subject><subject>Ku Autoantigen</subject><subject>Ku70</subject><subject>Nerve Growth Factors - genetics</subject><subject>Nerve Growth Factors - metabolism</subject><subject>Neurodegeneration</subject><subject>Neurons - metabolism</subject><subject>Neurotrophic Factor</subject><subject>NMR</subject><subject>Nuclear Magnetic Resonance, Biomolecular</subject><subject>Oxidopamine - adverse effects</subject><subject>Oxidopamine - pharmacology</subject><subject>Parkinson Disease</subject><subject>Parkinson Disease, Secondary - chemically induced</subject><subject>Parkinson Disease, Secondary - genetics</subject><subject>Parkinson Disease, Secondary - metabolism</subject><subject>Protein Structure and Folding</subject><subject>Protein Structure, Tertiary</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Rats</subject><subject>Structural Homology, Protein</subject><subject>Sympatholytics - adverse effects</subject><subject>Sympatholytics - pharmacokinetics</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUFv1DAQhS0EokvhzA1yAw5px3ZiJxekVcVSpG6RgJW4WY4z7rrKxsH2rtR_j5eUCg4IXyzP--bZ40fISwpnFGR1ftuZszU9niohefOILCg0vOQ1_f6YLAAYLVtWNyfkWYy3kFfV0qfkhFGopGxgQXZrjDganLZ6cKZYxhS8uUtY9hjcAfviGvfB5-K0zfJKm-RD8Xa9vF69Ky51LHSxGd2PPRZrNFs9urgrki--YDS5tpz8lHzKjb9cxvicPLF6iPjifj8lm9WHbxeX5dXnj58ullelqTmksuc1YMcoFR1rRNsJYZoGjATLbcd7yJKxFKiUFjvZdp1lRhpbi4oLYa3mp-T97Dvtux32BscU9KCm4HY63CmvnfpbGd1W3fiD4sAqKXg2eHNvEHyeLia1c9HgMOgR_T6qFiStQTL6X7LJEKtFLTN5PpMm-BgD2of3UFDHNFVOUx3TVHOauePVn2M88L_jy8DrGbDaK30TXFSbrwwoB9ryChqRiXYmMH_3wWFQ0bhj4L0LaJLqvfvn9T8BjY25IA</recordid><startdate>20110128</startdate><enddate>20110128</enddate><creator>Hellman, Maarit</creator><creator>Arumäe, Urmas</creator><creator>Yu, Li-ying</creator><creator>Lindholm, Päivi</creator><creator>Peränen, Johan</creator><creator>Saarma, Mart</creator><creator>Permi, Perttu</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><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>7TK</scope><scope>5PM</scope></search><sort><creationdate>20110128</creationdate><title>Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons</title><author>Hellman, Maarit ; Arumäe, Urmas ; Yu, Li-ying ; Lindholm, Päivi ; Peränen, Johan ; Saarma, Mart ; Permi, Perttu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c530t-d350eb2116b2869b66c880c70f3fb3d0b21cf10177feb79bbf2c7cf564366ffa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animals</topic><topic>Antigens, Nuclear - genetics</topic><topic>Antigens, Nuclear - metabolism</topic><topic>Apoptosis</topic><topic>Bax</topic><topic>bcl-2-Associated X Protein - genetics</topic><topic>bcl-2-Associated X Protein - metabolism</topic><topic>Cells, Cultured</topic><topic>Disease Models, Animal</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Humans</topic><topic>Ku Autoantigen</topic><topic>Ku70</topic><topic>Nerve Growth Factors - genetics</topic><topic>Nerve Growth Factors - metabolism</topic><topic>Neurodegeneration</topic><topic>Neurons - metabolism</topic><topic>Neurotrophic Factor</topic><topic>NMR</topic><topic>Nuclear Magnetic Resonance, Biomolecular</topic><topic>Oxidopamine - adverse effects</topic><topic>Oxidopamine - pharmacology</topic><topic>Parkinson Disease</topic><topic>Parkinson Disease, Secondary - chemically induced</topic><topic>Parkinson Disease, Secondary - genetics</topic><topic>Parkinson Disease, Secondary - metabolism</topic><topic>Protein Structure and Folding</topic><topic>Protein Structure, Tertiary</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Rats</topic><topic>Structural Homology, Protein</topic><topic>Sympatholytics - adverse effects</topic><topic>Sympatholytics - pharmacokinetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hellman, Maarit</creatorcontrib><creatorcontrib>Arumäe, Urmas</creatorcontrib><creatorcontrib>Yu, Li-ying</creatorcontrib><creatorcontrib>Lindholm, Päivi</creatorcontrib><creatorcontrib>Peränen, Johan</creatorcontrib><creatorcontrib>Saarma, Mart</creatorcontrib><creatorcontrib>Permi, Perttu</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of biological chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hellman, Maarit</au><au>Arumäe, Urmas</au><au>Yu, Li-ying</au><au>Lindholm, Päivi</au><au>Peränen, Johan</au><au>Saarma, Mart</au><au>Permi, Perttu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>2011-01-28</date><risdate>2011</risdate><volume>286</volume><issue>4</issue><spage>2675</spage><epage>2680</epage><pages>2675-2680</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><abstract>Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects neurons and repairs the Parkinson disease-like symptoms in a rat 6-hydroxydopamine model. We show a three-dimensional solution structure of human MANF that differs drastically from other neurotrophic factors. Remarkably, the C-terminal domain of MANF (C-MANF) is homologous to the SAP domain of Ku70, a well known inhibitor of proapoptotic Bax (Bcl-2-associated X protein). Cellular studies confirm that MANF and C-MANF protect neurons intracellularly as efficiently as Ku70.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21047780</pmid><doi>10.1074/jbc.M110.146738</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9258 |
| ispartof | The Journal of biological chemistry, 2011-01, Vol.286 (4), p.2675-2680 |
| issn | 0021-9258 1083-351X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3024763 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Antigens, Nuclear - genetics Antigens, Nuclear - metabolism Apoptosis Bax bcl-2-Associated X Protein - genetics bcl-2-Associated X Protein - metabolism Cells, Cultured Disease Models, Animal DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism Humans Ku Autoantigen Ku70 Nerve Growth Factors - genetics Nerve Growth Factors - metabolism Neurodegeneration Neurons - metabolism Neurotrophic Factor NMR Nuclear Magnetic Resonance, Biomolecular Oxidopamine - adverse effects Oxidopamine - pharmacology Parkinson Disease Parkinson Disease, Secondary - chemically induced Parkinson Disease, Secondary - genetics Parkinson Disease, Secondary - metabolism Protein Structure and Folding Protein Structure, Tertiary Proteins - genetics Proteins - metabolism Rats Structural Homology, Protein Sympatholytics - adverse effects Sympatholytics - pharmacokinetics |
| title | Mesencephalic Astrocyte-derived Neurotrophic Factor (MANF) Has a Unique Mechanism to Rescue Apoptotic Neurons |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T19%3A03%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mesencephalic%20Astrocyte-derived%20Neurotrophic%20Factor%20(MANF)%20Has%20a%20Unique%20Mechanism%20to%20Rescue%20Apoptotic%20Neurons&rft.jtitle=The%20Journal%20of%20biological%20chemistry&rft.au=Hellman,%20Maarit&rft.date=2011-01-28&rft.volume=286&rft.issue=4&rft.spage=2675&rft.epage=2680&rft.pages=2675-2680&rft.issn=0021-9258&rft.eissn=1083-351X&rft_id=info:doi/10.1074/jbc.M110.146738&rft_dat=%3Cproquest_pubme%3E872125657%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=872125657&rft_id=info:pmid/21047780&rft_els_id=S0021925820541409&rfr_iscdi=true |