Prions and Transmissible Spongiform Encephalopathy (TSE) Chemotherapeutics: A Common Mechanism for Anti-TSE Compounds?
Identifieur interne : 002228 ( Istex/Curation ); précédent : 002227; suivant : 002229Prions and Transmissible Spongiform Encephalopathy (TSE) Chemotherapeutics: A Common Mechanism for Anti-TSE Compounds?
Auteurs : B. Caughey [États-Unis] ; W. S. Caughey [États-Unis] ; D. A. Kocisko [États-Unis] ; K. S. Lee [États-Unis] ; J. R. Silveira [États-Unis] ; J. D. Morrey [États-Unis]Source :
- Accounts of Chemical Research [ 0001-4842 ] ; 2006.
Abstract
No validated treatments exist for transmissible spongiform encephalopathies (TSEs or prion diseases) in humans or livestock. The search for TSE therapeutics is complicated by persistent uncertainties about the nature of mammalian prions and their pathogenic mechanisms. In pursuit of anti-TSE drugs, we and others have focused primarily on blocking conversion of normal prion protein, PrPC, to the TSE-associated isoform, PrPSc. Recently developed high-throughput screens have hastened the identification of new inhibitors with strong in vivo anti-TSE activities such as porphyrins, phthalocyanines, and phosphorthioated oligonucleotides. New routes of administration have enhanced beneficial effects against established brain infections. Several different classes of TSE inhibitors share structural similarities, compete for the same site(s) on PrPC, and induce the clustering and internalization of PrPC from the cell surface. These activities may represent a common mechanism of action for these anti-TSE compounds.
Url:
DOI: 10.1021/ar050068p
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Caughey</name><affiliation wicri:level="2"><mods:affiliation>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan, Utah</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan</wicri:cityArea></affiliation><affiliation><mods:affiliation> National Institute of Allergy and Infectious Diseases.</mods:affiliation><wicri:noCountry code="no comma"> National Institute of Allergy and Infectious Diseases.</wicri:noCountry></affiliation><affiliation wicri:level="2"><mods:affiliation> Corresponding author. Mailing address: Rocky Mountain Labs, 903S. 4th St., Hamilton, MT 59840. Phone: (406) 363 9264. Fax: (406) 3639286. E-mail: bcaughey@nih.gov.</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea> Corresponding author. Mailing address: Rocky Mountain Labs, 903S. 4th St., Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Caughey, W S" sort="Caughey, W S" uniqKey="Caughey W" first="W. S." last="Caughey">W. S. 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Spongiform Encephalopathy
(TSE) Chemotherapeutics: A
Common Mechanism for Anti-TSE
Compounds?</title><author><name sortKey="Caughey, B" sort="Caughey, B" uniqKey="Caughey B" first="B." last="Caughey">B. Caughey</name><affiliation wicri:level="2"><mods:affiliation>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan, Utah</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan</wicri:cityArea></affiliation><affiliation><mods:affiliation> National Institute of Allergy and Infectious Diseases.</mods:affiliation></affiliation><affiliation wicri:level="2"><mods:affiliation> Corresponding author. Mailing address: Rocky Mountain Labs, 903S. 4th St., Hamilton, MT 59840. Phone: (406) 363 9264. Fax: (406) 3639286. E-mail: bcaughey@nih.gov.</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Montana</region></placeName><wicri:cityArea> Corresponding author. Mailing address: Rocky Mountain Labs, 903S. 4th St., Hamilton</wicri:cityArea></affiliation></author><author><name sortKey="Caughey, W S" sort="Caughey, W S" uniqKey="Caughey W" first="W. S." last="Caughey">W. S. Caughey</name><affiliation wicri:level="2"><mods:affiliation>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan, Utah</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan</wicri:cityArea></affiliation><affiliation><mods:affiliation> National Institute of Allergy and Infectious Diseases.</mods:affiliation></affiliation></author><author><name sortKey="Kocisko, D A" sort="Kocisko, D A" uniqKey="Kocisko D" first="D. A." last="Kocisko">D. A. Kocisko</name><affiliation wicri:level="2"><mods:affiliation>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan, Utah</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan</wicri:cityArea></affiliation><affiliation><mods:affiliation> National Institute of Allergy and Infectious Diseases.</mods:affiliation></affiliation></author><author><name sortKey="Lee, K S" sort="Lee, K S" uniqKey="Lee K" first="K. S." last="Lee">K. S. Lee</name><affiliation wicri:level="2"><mods:affiliation>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan, Utah</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan</wicri:cityArea></affiliation><affiliation><mods:affiliation> National Institute of Allergy and Infectious Diseases.</mods:affiliation></affiliation></author><author><name sortKey="Silveira, J R" sort="Silveira, J R" uniqKey="Silveira J" first="J. R." last="Silveira">J. R. Silveira</name><affiliation wicri:level="2"><mods:affiliation>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan, Utah</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan</wicri:cityArea></affiliation><affiliation><mods:affiliation> National Institute of Allergy and Infectious Diseases.</mods:affiliation></affiliation></author><author><name sortKey="Morrey, J D" sort="Morrey, J D" uniqKey="Morrey J" first="J. D." last="Morrey">J. D. Morrey</name><affiliation wicri:level="2"><mods:affiliation>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan, Utah</mods:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Utah</region></placeName><wicri:cityArea>National Institute of Allergy and Infectious Diseases,National Institutes of Health, Rocky Mountain Laboratories,Hamilton, Montana, and Institute for Antiviral Research,Animal, Dairy and Veterinary Sciences Department, UtahState University, Logan</wicri:cityArea></affiliation><affiliation><mods:affiliation> Utah State University.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Accounts of Chemical Research</title><title level="j" type="abbrev">Acc. Chem. Res.</title><idno type="ISSN">0001-4842</idno><idno type="eISSN">1520-4898</idno><imprint><publisher>American Chemical Society</publisher><date type="e-published">2006</date><date type="published">2006</date><biblScope unit="vol">39</biblScope><biblScope unit="issue">9</biblScope><biblScope unit="page" from="646">646</biblScope><biblScope unit="page" to="653">653</biblScope></imprint><idno type="ISSN">0001-4842</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0001-4842</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">No validated treatments exist for transmissible spongiform encephalopathies (TSEs or prion diseases) in humans or livestock. The search for TSE therapeutics is complicated by persistent uncertainties about the nature of mammalian prions and their pathogenic mechanisms. In pursuit of anti-TSE drugs, we and others have focused primarily on blocking conversion of normal prion protein, PrPC, to the TSE-associated isoform, PrPSc. Recently developed high-throughput screens have hastened the identification of new inhibitors with strong in vivo anti-TSE activities such as porphyrins, phthalocyanines, and phosphorthioated oligonucleotides. New routes of administration have enhanced beneficial effects against established brain infections. Several different classes of TSE inhibitors share structural similarities, compete for the same site(s) on PrPC, and induce the clustering and internalization of PrPC from the cell surface. These activities may represent a common mechanism of action for these anti-TSE compounds.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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