Neuroprotective Strategy for Alzheimer Disease: Intranasal Administration of a Fatty Neuropeptide
Neurodegenerative diseases, in which neuronal cells disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1996-01, Vol.93 (1), p.427-432 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 432 |
|---|---|
| container_issue | 1 |
| container_start_page | 427 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 93 |
| creator | Gozes, I. Bardea, A. Reshef, A. Zamostiano, R. Zhukovsky, S. Rubinraut, S. Fridikin, M. Brenneman, D. E. |
| description | Neurodegenerative diseases, in which neuronal cells disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearylnorleucine17]VIP ([St-Nle17]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The β -amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the β -amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade. These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain. |
| doi_str_mv | 10.1073/pnas.93.1.427 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_15831385</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>38383</jstor_id><sourcerecordid>38383</sourcerecordid><originalsourceid>FETCH-LOGICAL-c574t-c05887c45d978d5da51050931b67e1e668c10487629aeb98c2645332d4f38eac3</originalsourceid><addsrcrecordid>eNp9kU1v1DAURS0EKkNhyQaBZCGVXQZ_Jg7qZlRaWqmCBbC2PM5L61ESB9upOvx6HM10BF0gL7w45z4_6yL0mpIlJRX_OA4mLmu-pEvBqidoQUlNi1LU5ClaEMKqQgkmnqMXMW4IIbVU5AgdKSlZKfkCma8wBT8Gn8Amdwf4ewomwc0Wtz7gVff7FlwPAX92EUyET_hqyEJ-0nR41fRucHEOOD9g32KDL0xKW7wbCmNyDbxEz1rTRXi1v4_Rz4vzH2eXxfW3L1dnq-vCykqkwhKpVGWFbOpKNbIxkhJJak7XZQUUylJZSoSqSlYbWNfKslJIzlkjWq7AWH6MTndzx2ndQ2NhXrTTY3C9CVvtjdP_ksHd6ht_pwVhkub4h308-F8TxKR7Fy10nRnAT1FTqTjlSmbx_SNx46cw5K9pRiiXspIsS8VOssHHGKA97EGJnmvTc2265prqXFv23_29_MHe95T5yZ7PsQf6ENft1HUJ7lP23v7Hy_jNDm9i8uHAucqH_wGiZ7T5</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>201355752</pqid></control><display><type>article</type><title>Neuroprotective Strategy for Alzheimer Disease: Intranasal Administration of a Fatty Neuropeptide</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Gozes, I. ; Bardea, A. ; Reshef, A. ; Zamostiano, R. ; Zhukovsky, S. ; Rubinraut, S. ; Fridikin, M. ; Brenneman, D. E.</creator><creatorcontrib>Gozes, I. ; Bardea, A. ; Reshef, A. ; Zamostiano, R. ; Zhukovsky, S. ; Rubinraut, S. ; Fridikin, M. ; Brenneman, D. E.</creatorcontrib><description>Neurodegenerative diseases, in which neuronal cells disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearylnorleucine17]VIP ([St-Nle17]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The β -amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the β -amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade. These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.93.1.427</identifier><identifier>PMID: 8552653</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Administration, Intranasal ; Alzheimer Disease - prevention & control ; Alzheimer's disease ; Alzheimers disease ; Amino acids ; Amyloid beta-Peptides - antagonists & inhibitors ; Animals ; Aziridines - pharmacology ; Biology ; Brain ; Cell death ; Cell Death - drug effects ; Cells, Cultured ; Cerebral cortex ; Choline - analogs & derivatives ; Choline - pharmacology ; Cholinergics ; Intranasal administration ; Learning ; Learning - drug effects ; Lipids ; Male ; Memory ; Memory - drug effects ; Neurology ; Neuromuscular Blocking Agents ; Neurons ; Neurons - cytology ; Parasympatholytics - pharmacology ; Peptides ; Rats ; Rats, Wistar ; Solubility ; Structure-Activity Relationship ; Vasoactive Intestinal Peptide - pharmacology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1996-01, Vol.93 (1), p.427-432</ispartof><rights>Copyright 1996 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Jan 9, 1996</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c574t-c05887c45d978d5da51050931b67e1e668c10487629aeb98c2645332d4f38eac3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/93/1.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/38383$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/38383$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,315,728,781,785,804,886,27929,27930,53796,53798,58022,58255</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8552653$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gozes, I.</creatorcontrib><creatorcontrib>Bardea, A.</creatorcontrib><creatorcontrib>Reshef, A.</creatorcontrib><creatorcontrib>Zamostiano, R.</creatorcontrib><creatorcontrib>Zhukovsky, S.</creatorcontrib><creatorcontrib>Rubinraut, S.</creatorcontrib><creatorcontrib>Fridikin, M.</creatorcontrib><creatorcontrib>Brenneman, D. E.</creatorcontrib><title>Neuroprotective Strategy for Alzheimer Disease: Intranasal Administration of a Fatty Neuropeptide</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Neurodegenerative diseases, in which neuronal cells disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearylnorleucine17]VIP ([St-Nle17]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The β -amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the β -amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade. These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain.</description><subject>Administration, Intranasal</subject><subject>Alzheimer Disease - prevention & control</subject><subject>Alzheimer's disease</subject><subject>Alzheimers disease</subject><subject>Amino acids</subject><subject>Amyloid beta-Peptides - antagonists & inhibitors</subject><subject>Animals</subject><subject>Aziridines - pharmacology</subject><subject>Biology</subject><subject>Brain</subject><subject>Cell death</subject><subject>Cell Death - drug effects</subject><subject>Cells, Cultured</subject><subject>Cerebral cortex</subject><subject>Choline - analogs & derivatives</subject><subject>Choline - pharmacology</subject><subject>Cholinergics</subject><subject>Intranasal administration</subject><subject>Learning</subject><subject>Learning - drug effects</subject><subject>Lipids</subject><subject>Male</subject><subject>Memory</subject><subject>Memory - drug effects</subject><subject>Neurology</subject><subject>Neuromuscular Blocking Agents</subject><subject>Neurons</subject><subject>Neurons - cytology</subject><subject>Parasympatholytics - pharmacology</subject><subject>Peptides</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Solubility</subject><subject>Structure-Activity Relationship</subject><subject>Vasoactive Intestinal Peptide - pharmacology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAURS0EKkNhyQaBZCGVXQZ_Jg7qZlRaWqmCBbC2PM5L61ESB9upOvx6HM10BF0gL7w45z4_6yL0mpIlJRX_OA4mLmu-pEvBqidoQUlNi1LU5ClaEMKqQgkmnqMXMW4IIbVU5AgdKSlZKfkCma8wBT8Gn8Amdwf4ewomwc0Wtz7gVff7FlwPAX92EUyET_hqyEJ-0nR41fRucHEOOD9g32KDL0xKW7wbCmNyDbxEz1rTRXi1v4_Rz4vzH2eXxfW3L1dnq-vCykqkwhKpVGWFbOpKNbIxkhJJak7XZQUUylJZSoSqSlYbWNfKslJIzlkjWq7AWH6MTndzx2ndQ2NhXrTTY3C9CVvtjdP_ksHd6ht_pwVhkub4h308-F8TxKR7Fy10nRnAT1FTqTjlSmbx_SNx46cw5K9pRiiXspIsS8VOssHHGKA97EGJnmvTc2265prqXFv23_29_MHe95T5yZ7PsQf6ENft1HUJ7lP23v7Hy_jNDm9i8uHAucqH_wGiZ7T5</recordid><startdate>19960109</startdate><enddate>19960109</enddate><creator>Gozes, I.</creator><creator>Bardea, A.</creator><creator>Reshef, A.</creator><creator>Zamostiano, R.</creator><creator>Zhukovsky, S.</creator><creator>Rubinraut, S.</creator><creator>Fridikin, M.</creator><creator>Brenneman, D. E.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>5PM</scope></search><sort><creationdate>19960109</creationdate><title>Neuroprotective Strategy for Alzheimer Disease: Intranasal Administration of a Fatty Neuropeptide</title><author>Gozes, I. ; Bardea, A. ; Reshef, A. ; Zamostiano, R. ; Zhukovsky, S. ; Rubinraut, S. ; Fridikin, M. ; Brenneman, D. E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c574t-c05887c45d978d5da51050931b67e1e668c10487629aeb98c2645332d4f38eac3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Administration, Intranasal</topic><topic>Alzheimer Disease - prevention & control</topic><topic>Alzheimer's disease</topic><topic>Alzheimers disease</topic><topic>Amino acids</topic><topic>Amyloid beta-Peptides - antagonists & inhibitors</topic><topic>Animals</topic><topic>Aziridines - pharmacology</topic><topic>Biology</topic><topic>Brain</topic><topic>Cell death</topic><topic>Cell Death - drug effects</topic><topic>Cells, Cultured</topic><topic>Cerebral cortex</topic><topic>Choline - analogs & derivatives</topic><topic>Choline - pharmacology</topic><topic>Cholinergics</topic><topic>Intranasal administration</topic><topic>Learning</topic><topic>Learning - drug effects</topic><topic>Lipids</topic><topic>Male</topic><topic>Memory</topic><topic>Memory - drug effects</topic><topic>Neurology</topic><topic>Neuromuscular Blocking Agents</topic><topic>Neurons</topic><topic>Neurons - cytology</topic><topic>Parasympatholytics - pharmacology</topic><topic>Peptides</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Solubility</topic><topic>Structure-Activity Relationship</topic><topic>Vasoactive Intestinal Peptide - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gozes, I.</creatorcontrib><creatorcontrib>Bardea, A.</creatorcontrib><creatorcontrib>Reshef, A.</creatorcontrib><creatorcontrib>Zamostiano, R.</creatorcontrib><creatorcontrib>Zhukovsky, S.</creatorcontrib><creatorcontrib>Rubinraut, S.</creatorcontrib><creatorcontrib>Fridikin, M.</creatorcontrib><creatorcontrib>Brenneman, D. E.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gozes, I.</au><au>Bardea, A.</au><au>Reshef, A.</au><au>Zamostiano, R.</au><au>Zhukovsky, S.</au><au>Rubinraut, S.</au><au>Fridikin, M.</au><au>Brenneman, D. E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroprotective Strategy for Alzheimer Disease: Intranasal Administration of a Fatty Neuropeptide</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1996-01-09</date><risdate>1996</risdate><volume>93</volume><issue>1</issue><spage>427</spage><epage>432</epage><pages>427-432</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Neurodegenerative diseases, in which neuronal cells disintegrate, bring about deteriorations in cognitive functions as is evidenced in millions of Alzheimer patients. A major neuropeptide, vasoactive intestinal peptide (VIP), has been shown to be neuroprotective and to play an important role in the acquisition of learning and memory. A potent lipophilic analogue to VIP now has been synthesized, [stearylnorleucine17]VIP ([St-Nle17]VIP), that exhibited neuroprotection in model systems related to Alzheimer disease. The β -amyloid peptide is a major component of the cerebral amyloid plaque in Alzheimer disease and has been shown to be neurotoxic. We have found a 70% loss in the number of neurons in rat cerebral cortical cultures treated with the β -amyloid peptide (amino acids 25-35) in comparison to controls. This cell death was completely prevented by cotreatment with 0.1 pM [St-Nle17]VIP. Furthermore, characteristic deficiencies in Alzheimer disease result from death of cholinergic neurons. Rats treated with a cholinergic blocker (ethylcholine aziridium) have been used as a model for cholinergic deficits. St-Nle-VIP injected intracerebroventricularly or delivered intranasally prevented impairments in spatial learning and memory associated with cholinergic blockade. These studies suggest both an unusual therapeutic strategy for treatment of Alzheimer deficiencies and a means for noninvasive peptide administration to the brain.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>8552653</pmid><doi>10.1073/pnas.93.1.427</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1996-01, Vol.93 (1), p.427-432 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_15831385 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Administration, Intranasal Alzheimer Disease - prevention & control Alzheimer's disease Alzheimers disease Amino acids Amyloid beta-Peptides - antagonists & inhibitors Animals Aziridines - pharmacology Biology Brain Cell death Cell Death - drug effects Cells, Cultured Cerebral cortex Choline - analogs & derivatives Choline - pharmacology Cholinergics Intranasal administration Learning Learning - drug effects Lipids Male Memory Memory - drug effects Neurology Neuromuscular Blocking Agents Neurons Neurons - cytology Parasympatholytics - pharmacology Peptides Rats Rats, Wistar Solubility Structure-Activity Relationship Vasoactive Intestinal Peptide - pharmacology |
| title | Neuroprotective Strategy for Alzheimer Disease: Intranasal Administration of a Fatty Neuropeptide |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T01%3A55%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neuroprotective%20Strategy%20for%20Alzheimer%20Disease:%20Intranasal%20Administration%20of%20a%20Fatty%20Neuropeptide&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Gozes,%20I.&rft.date=1996-01-09&rft.volume=93&rft.issue=1&rft.spage=427&rft.epage=432&rft.pages=427-432&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.93.1.427&rft_dat=%3Cjstor_proqu%3E38383%3C/jstor_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201355752&rft_id=info:pmid/8552653&rft_jstor_id=38383&rfr_iscdi=true |