A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats
Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its...
Gespeichert in:
| Veröffentlicht in: | The Journal of neuroscience 2008-03, Vol.28 (11), p.2698-2709 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2709 |
|---|---|
| container_issue | 11 |
| container_start_page | 2698 |
| container_title | The Journal of neuroscience |
| container_volume | 28 |
| creator | Colangelo, Anna Maria Bianco, Maria Rosaria Vitagliano, Luigi Cavaliere, Carlo Cirillo, Giovanni De Gioia, Luca Diana, Donatella Colombo, Daniele Redaelli, Cristina Zaccaro, Laura Morelli, Giancarlo Papa, Michele Sarmientos, Paolo Alberghina, Lilia Martegani, Enzo |
| description | Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 mum. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide. |
| doi_str_mv | 10.1523/JNEUROSCI.5201-07.2008 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6670672</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20539099</sourcerecordid><originalsourceid>FETCH-LOGICAL-c566t-1e3bab02a8ddd76a935a3e3d9a6594198d0bdaec9ce87da657f47f2186023f073</originalsourceid><addsrcrecordid>eNpVkVFP2zAUhS20CTrYX0B52p7SXduJHb9MqipgTAUmGM-WazvEUxJ3tkvEv8dVKzYkX1ny-e651j0InWOY45rQbz9vLx7v7x6W1_OaAC6BzwlAc4RmWRUlqQB_QDMgHEpW8eoEfYrxDwBwwPwYneCGUk6FmKHVori1U67wbIur4KfUFZdKJx_KGzfY5HTxy26SM7ZY6OQy5MdMb4PfqNTtVOXGIp97leIZ-tiqPtrPh_sUPV5e_F7-KFd3V9fLxarUNWOpxJau1RqIaowxnClBa0UtNUKxWlRYNAbWRlkttG24yY-8rXhLcMOA0BY4PUXf976b7XqwRtsxBdXLTXCDCi_SKyffK6Pr5JN_loxxYJxkgy8Hg-D_bm1McnBR275Xo_XbKAnUVIAQGWR7UAcfY7Dt2xAMcheEfAtC7oKQwOUuiNx4_v8X_7UdNp-Br3ugc0_d5IKVcVB9n3Esp2kijcRYEiYa-grGsZNe</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20539099</pqid></control><display><type>article</type><title>A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats</title><source>MEDLINE</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Colangelo, Anna Maria ; Bianco, Maria Rosaria ; Vitagliano, Luigi ; Cavaliere, Carlo ; Cirillo, Giovanni ; De Gioia, Luca ; Diana, Donatella ; Colombo, Daniele ; Redaelli, Cristina ; Zaccaro, Laura ; Morelli, Giancarlo ; Papa, Michele ; Sarmientos, Paolo ; Alberghina, Lilia ; Martegani, Enzo</creator><creatorcontrib>Colangelo, Anna Maria ; Bianco, Maria Rosaria ; Vitagliano, Luigi ; Cavaliere, Carlo ; Cirillo, Giovanni ; De Gioia, Luca ; Diana, Donatella ; Colombo, Daniele ; Redaelli, Cristina ; Zaccaro, Laura ; Morelli, Giancarlo ; Papa, Michele ; Sarmientos, Paolo ; Alberghina, Lilia ; Martegani, Enzo</creatorcontrib><description>Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 mum. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide.</description><identifier>ISSN: 0270-6474</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.5201-07.2008</identifier><identifier>PMID: 18337399</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Animals ; Biomimetic Materials - pharmacology ; Biomimetic Materials - therapeutic use ; Cells, Cultured ; Chick Embryo ; Humans ; Male ; Mice ; Nerve Growth Factor - agonists ; Nerve Growth Factor - pharmacology ; Nerve Growth Factor - therapeutic use ; Pain - drug therapy ; Pain - metabolism ; Pain Measurement - drug effects ; Pain Measurement - methods ; PC12 Cells ; Peptides - chemical synthesis ; Peptides - pharmacology ; Peptides - therapeutic use ; Peripheral Nervous System Diseases - drug therapy ; Peripheral Nervous System Diseases - metabolism ; Rats ; Rats, Sprague-Dawley ; Sciatic Neuropathy - drug therapy ; Sciatic Neuropathy - metabolism</subject><ispartof>The Journal of neuroscience, 2008-03, Vol.28 (11), p.2698-2709</ispartof><rights>Copyright © 2008 Society for Neuroscience 0270-6474/08/282698-12$15.00/0 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c566t-1e3bab02a8ddd76a935a3e3d9a6594198d0bdaec9ce87da657f47f2186023f073</citedby><cites>FETCH-LOGICAL-c566t-1e3bab02a8ddd76a935a3e3d9a6594198d0bdaec9ce87da657f47f2186023f073</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/PMC6670672/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6670672/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18337399$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Colangelo, Anna Maria</creatorcontrib><creatorcontrib>Bianco, Maria Rosaria</creatorcontrib><creatorcontrib>Vitagliano, Luigi</creatorcontrib><creatorcontrib>Cavaliere, Carlo</creatorcontrib><creatorcontrib>Cirillo, Giovanni</creatorcontrib><creatorcontrib>De Gioia, Luca</creatorcontrib><creatorcontrib>Diana, Donatella</creatorcontrib><creatorcontrib>Colombo, Daniele</creatorcontrib><creatorcontrib>Redaelli, Cristina</creatorcontrib><creatorcontrib>Zaccaro, Laura</creatorcontrib><creatorcontrib>Morelli, Giancarlo</creatorcontrib><creatorcontrib>Papa, Michele</creatorcontrib><creatorcontrib>Sarmientos, Paolo</creatorcontrib><creatorcontrib>Alberghina, Lilia</creatorcontrib><creatorcontrib>Martegani, Enzo</creatorcontrib><title>A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 mum. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide.</description><subject>Animals</subject><subject>Biomimetic Materials - pharmacology</subject><subject>Biomimetic Materials - therapeutic use</subject><subject>Cells, Cultured</subject><subject>Chick Embryo</subject><subject>Humans</subject><subject>Male</subject><subject>Mice</subject><subject>Nerve Growth Factor - agonists</subject><subject>Nerve Growth Factor - pharmacology</subject><subject>Nerve Growth Factor - therapeutic use</subject><subject>Pain - drug therapy</subject><subject>Pain - metabolism</subject><subject>Pain Measurement - drug effects</subject><subject>Pain Measurement - methods</subject><subject>PC12 Cells</subject><subject>Peptides - chemical synthesis</subject><subject>Peptides - pharmacology</subject><subject>Peptides - therapeutic use</subject><subject>Peripheral Nervous System Diseases - drug therapy</subject><subject>Peripheral Nervous System Diseases - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sciatic Neuropathy - drug therapy</subject><subject>Sciatic Neuropathy - metabolism</subject><issn>0270-6474</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkVFP2zAUhS20CTrYX0B52p7SXduJHb9MqipgTAUmGM-WazvEUxJ3tkvEv8dVKzYkX1ny-e651j0InWOY45rQbz9vLx7v7x6W1_OaAC6BzwlAc4RmWRUlqQB_QDMgHEpW8eoEfYrxDwBwwPwYneCGUk6FmKHVori1U67wbIur4KfUFZdKJx_KGzfY5HTxy26SM7ZY6OQy5MdMb4PfqNTtVOXGIp97leIZ-tiqPtrPh_sUPV5e_F7-KFd3V9fLxarUNWOpxJau1RqIaowxnClBa0UtNUKxWlRYNAbWRlkttG24yY-8rXhLcMOA0BY4PUXf976b7XqwRtsxBdXLTXCDCi_SKyffK6Pr5JN_loxxYJxkgy8Hg-D_bm1McnBR275Xo_XbKAnUVIAQGWR7UAcfY7Dt2xAMcheEfAtC7oKQwOUuiNx4_v8X_7UdNp-Br3ugc0_d5IKVcVB9n3Esp2kijcRYEiYa-grGsZNe</recordid><startdate>20080312</startdate><enddate>20080312</enddate><creator>Colangelo, Anna Maria</creator><creator>Bianco, Maria Rosaria</creator><creator>Vitagliano, Luigi</creator><creator>Cavaliere, Carlo</creator><creator>Cirillo, Giovanni</creator><creator>De Gioia, Luca</creator><creator>Diana, Donatella</creator><creator>Colombo, Daniele</creator><creator>Redaelli, Cristina</creator><creator>Zaccaro, Laura</creator><creator>Morelli, Giancarlo</creator><creator>Papa, Michele</creator><creator>Sarmientos, Paolo</creator><creator>Alberghina, Lilia</creator><creator>Martegani, Enzo</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</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>7TK</scope><scope>5PM</scope></search><sort><creationdate>20080312</creationdate><title>A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats</title><author>Colangelo, Anna Maria ; Bianco, Maria Rosaria ; Vitagliano, Luigi ; Cavaliere, Carlo ; Cirillo, Giovanni ; De Gioia, Luca ; Diana, Donatella ; Colombo, Daniele ; Redaelli, Cristina ; Zaccaro, Laura ; Morelli, Giancarlo ; Papa, Michele ; Sarmientos, Paolo ; Alberghina, Lilia ; Martegani, Enzo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c566t-1e3bab02a8ddd76a935a3e3d9a6594198d0bdaec9ce87da657f47f2186023f073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biomimetic Materials - pharmacology</topic><topic>Biomimetic Materials - therapeutic use</topic><topic>Cells, Cultured</topic><topic>Chick Embryo</topic><topic>Humans</topic><topic>Male</topic><topic>Mice</topic><topic>Nerve Growth Factor - agonists</topic><topic>Nerve Growth Factor - pharmacology</topic><topic>Nerve Growth Factor - therapeutic use</topic><topic>Pain - drug therapy</topic><topic>Pain - metabolism</topic><topic>Pain Measurement - drug effects</topic><topic>Pain Measurement - methods</topic><topic>PC12 Cells</topic><topic>Peptides - chemical synthesis</topic><topic>Peptides - pharmacology</topic><topic>Peptides - therapeutic use</topic><topic>Peripheral Nervous System Diseases - drug therapy</topic><topic>Peripheral Nervous System Diseases - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sciatic Neuropathy - drug therapy</topic><topic>Sciatic Neuropathy - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Colangelo, Anna Maria</creatorcontrib><creatorcontrib>Bianco, Maria Rosaria</creatorcontrib><creatorcontrib>Vitagliano, Luigi</creatorcontrib><creatorcontrib>Cavaliere, Carlo</creatorcontrib><creatorcontrib>Cirillo, Giovanni</creatorcontrib><creatorcontrib>De Gioia, Luca</creatorcontrib><creatorcontrib>Diana, Donatella</creatorcontrib><creatorcontrib>Colombo, Daniele</creatorcontrib><creatorcontrib>Redaelli, Cristina</creatorcontrib><creatorcontrib>Zaccaro, Laura</creatorcontrib><creatorcontrib>Morelli, Giancarlo</creatorcontrib><creatorcontrib>Papa, Michele</creatorcontrib><creatorcontrib>Sarmientos, Paolo</creatorcontrib><creatorcontrib>Alberghina, Lilia</creatorcontrib><creatorcontrib>Martegani, Enzo</creatorcontrib><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 neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Colangelo, Anna Maria</au><au>Bianco, Maria Rosaria</au><au>Vitagliano, Luigi</au><au>Cavaliere, Carlo</au><au>Cirillo, Giovanni</au><au>De Gioia, Luca</au><au>Diana, Donatella</au><au>Colombo, Daniele</au><au>Redaelli, Cristina</au><au>Zaccaro, Laura</au><au>Morelli, Giancarlo</au><au>Papa, Michele</au><au>Sarmientos, Paolo</au><au>Alberghina, Lilia</au><au>Martegani, Enzo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2008-03-12</date><risdate>2008</risdate><volume>28</volume><issue>11</issue><spage>2698</spage><epage>2709</epage><pages>2698-2709</pages><issn>0270-6474</issn><eissn>1529-2401</eissn><abstract>Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A (TrkA) complex, site-directed mutagenesis studies and results from chemical modification of amino acid residues have identified loop 1, loop 4, and the N-terminal region of the NGF molecule as the most relevant for its biological activity. We synthesized several peptides mimicking the two loops (1 and 4) linked together with an appropriate spacer, with or without the N-terminal region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity at a concentration as low as 3 mum. They induced differentiation of chick dorsal root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB, receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown to reduce neuropathic behavior and restore neuronal function in a rat model of peripheral neuropathic pain, thereby suggesting a potential therapeutic role for this NGF-mimetic peptide.</abstract><cop>United States</cop><pub>Soc Neuroscience</pub><pmid>18337399</pmid><doi>10.1523/JNEUROSCI.5201-07.2008</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0270-6474 |
| ispartof | The Journal of neuroscience, 2008-03, Vol.28 (11), p.2698-2709 |
| issn | 0270-6474 1529-2401 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6670672 |
| source | MEDLINE; PubMed Central; EZB Electronic Journals Library |
| subjects | Animals Biomimetic Materials - pharmacology Biomimetic Materials - therapeutic use Cells, Cultured Chick Embryo Humans Male Mice Nerve Growth Factor - agonists Nerve Growth Factor - pharmacology Nerve Growth Factor - therapeutic use Pain - drug therapy Pain - metabolism Pain Measurement - drug effects Pain Measurement - methods PC12 Cells Peptides - chemical synthesis Peptides - pharmacology Peptides - therapeutic use Peripheral Nervous System Diseases - drug therapy Peripheral Nervous System Diseases - metabolism Rats Rats, Sprague-Dawley Sciatic Neuropathy - drug therapy Sciatic Neuropathy - metabolism |
| title | A New Nerve Growth Factor-Mimetic Peptide Active on Neuropathic Pain in Rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-10T18%3A08%3A53IST&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=A%20New%20Nerve%20Growth%20Factor-Mimetic%20Peptide%20Active%20on%20Neuropathic%20Pain%20in%20Rats&rft.jtitle=The%20Journal%20of%20neuroscience&rft.au=Colangelo,%20Anna%20Maria&rft.date=2008-03-12&rft.volume=28&rft.issue=11&rft.spage=2698&rft.epage=2709&rft.pages=2698-2709&rft.issn=0270-6474&rft.eissn=1529-2401&rft_id=info:doi/10.1523/JNEUROSCI.5201-07.2008&rft_dat=%3Cproquest_pubme%3E20539099%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=20539099&rft_id=info:pmid/18337399&rfr_iscdi=true |