Pituitary Adenylate Cyclase-Activating Polypeptide: Focus on Structure-Activity Relationships of a Neuroprotective Peptide
Identifieur interne : 000208 ( France/Analysis ); précédent : 000207; suivant : 000209Pituitary Adenylate Cyclase-Activating Polypeptide: Focus on Structure-Activity Relationships of a Neuroprotective Peptide
Auteurs : S. Bourgault [Canada, France] ; D. Vaudry [France] ; A. Dejda [Canada, France] ; N. D. Doan [Canada, France] ; H. Vaudry [France] ; A. Fournier [Canada, France]Source :
- Current medicinal chemistry [ 0929-8673 ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
- Affinity, Agonist, Degenerative disease, G protein coupled receptor, In vitro, In vivo, Mechanism of action, Nervous system diseases, Neuron, Neuroprotective agent, PAC1 receptor, Pituitary adenylate cyclase activating peptide, Review, Secondary structure, Selectivity, Structure activity relation, Treatment.
Abstract
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was initially isolated from hypothalamus extracts on the basis of its ability to stimulate the production of cAMP in cultured pituitary cells. Recent studies have shown that PACAP exerts potent neuroprotective effects not only in vitro but also in in vivo models of Parkinson's disease, Huntington's disease, traumatic brain injury and stroke. The protective effects of PACAP are based on its capacity to prevent neuronal apoptosis by acting directly on neurons or indirectly through the release of neuroprotective factors by astrocytes. These biological activities are mainly mediated through activation of the PAC 1 receptor which is currently considered as a potential target for the treatment of neurodegenerative diseases. However, the use of native PACAP, the endogenous ligand of PAC1, as an efficient neuroprotective drug is actually limited by its rapid degradation. Moreover, injection of PACAP to human induces peripheral side effects which are mainly mediated through VPAC I and VPAC2 receptors. Strategies to overcome these compromising conditions include the development of metabolically stable analogs of PACAP acting as selective agonists of the PAC1 receptor. This review presents an overview of the structure-activity relationships of PACAP and summarizes the molecular and conformational requirements for activation of PAC1 receptor. The applicability of PACAP analogs as therapeutic agents for treatment of neurodegenerative diseases is also discussed.
Affiliations:
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Pascal:10-0131039Le document en format XML
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Bourgault</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 boul. des Prairies</s1><s2>Ville de Laval, Qc, H7V 1B7</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ville de Laval, Qc, H7V 1B7</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Neuroendocrinologie Cellulaire et Moléculaire, INSERM U413, Université de Rouen</s1><s2>76821 Mont-Saint-Aignan</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>76821 Mont-Saint-Aignan</wicri:noRegion><wicri:noRegion>Université de Rouen</wicri:noRegion><placeName><settlement type="city">Rouen</settlement><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region></placeName><orgName type="university">Université de Rouen</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Vaudry, D" sort="Vaudry, D" uniqKey="Vaudry D" first="D." last="Vaudry">D. 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Dejda</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 boul. des Prairies</s1><s2>Ville de Laval, Qc, H7V 1B7</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ville de Laval, Qc, H7V 1B7</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Doan, N D" sort="Doan, N D" uniqKey="Doan N" first="N. D." last="Doan">N. D. Doan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 boul. des Prairies</s1><s2>Ville de Laval, Qc, H7V 1B7</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ville de Laval, Qc, H7V 1B7</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Vaudry, H" sort="Vaudry, H" uniqKey="Vaudry H" first="H." last="Vaudry">H. 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Bourgault</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 boul. des Prairies</s1><s2>Ville de Laval, Qc, H7V 1B7</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ville de Laval, Qc, H7V 1B7</wicri:noRegion></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Neuroendocrinologie Cellulaire et Moléculaire, INSERM U413, Université de Rouen</s1><s2>76821 Mont-Saint-Aignan</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>76821 Mont-Saint-Aignan</wicri:noRegion><wicri:noRegion>Université de Rouen</wicri:noRegion><placeName><settlement type="city">Rouen</settlement><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region></placeName><orgName type="university">Université de Rouen</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Vaudry, D" sort="Vaudry, D" uniqKey="Vaudry D" first="D." last="Vaudry">D. Vaudry</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Neuroendocrinologie Cellulaire et Moléculaire, INSERM U413, Université de Rouen</s1><s2>76821 Mont-Saint-Aignan</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>76821 Mont-Saint-Aignan</wicri:noRegion><wicri:noRegion>Université de Rouen</wicri:noRegion><placeName><settlement type="city">Rouen</settlement><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region></placeName><orgName type="university">Université de Rouen</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Dejda, A" sort="Dejda, A" uniqKey="Dejda A" first="A." last="Dejda">A. Dejda</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 boul. des Prairies</s1><s2>Ville de Laval, Qc, H7V 1B7</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ville de Laval, Qc, H7V 1B7</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Doan, N D" sort="Doan, N D" uniqKey="Doan N" first="N. D." last="Doan">N. D. Doan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 boul. des Prairies</s1><s2>Ville de Laval, Qc, H7V 1B7</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ville de Laval, Qc, H7V 1B7</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Vaudry, H" sort="Vaudry, H" uniqKey="Vaudry H" first="H." last="Vaudry">H. Vaudry</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Laboratoire de Neuroendocrinologie Cellulaire et Moléculaire, INSERM U413, Université de Rouen</s1><s2>76821 Mont-Saint-Aignan</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>76821 Mont-Saint-Aignan</wicri:noRegion><wicri:noRegion>Université de Rouen</wicri:noRegion><placeName><settlement type="city">Rouen</settlement><region type="region" nuts="2">Région Normandie</region><region type="old region" nuts="2">Haute-Normandie</region></placeName><orgName type="university">Université de Rouen</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author><author><name sortKey="Fournier, A" sort="Fournier, A" uniqKey="Fournier A" first="A." last="Fournier">A. Fournier</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>INRS-Institut Armand-Frappier, Institut National de la Recherche Scientifique, 531 boul. des Prairies</s1><s2>Ville de Laval, Qc, H7V 1B7</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Ville de Laval, Qc, H7V 1B7</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</s1><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion><wicri:noRegion>International Associated Laboratory Samuel de Champlain (INSERM- INRS)</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Current medicinal chemistry</title><title level="j" type="abbreviated">Curr. med. chem.</title><idno type="ISSN">0929-8673</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Current medicinal chemistry</title><title level="j" type="abbreviated">Curr. med. chem.</title><idno type="ISSN">0929-8673</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Affinity</term><term>Agonist</term><term>Degenerative disease</term><term>G protein coupled receptor</term><term>In vitro</term><term>In vivo</term><term>Mechanism of action</term><term>Nervous system diseases</term><term>Neuron</term><term>Neuroprotective agent</term><term>PAC1 receptor</term><term>Pituitary adenylate cyclase activating peptide</term><term>Review</term><term>Secondary structure</term><term>Selectivity</term><term>Structure activity relation</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Peptide PACAP</term><term>Relation structure activité</term><term>Neuroprotecteur</term><term>Récepteur PAC1</term><term>Maladie dégénérative</term><term>Pathologie du système nerveux</term><term>In vitro</term><term>In vivo</term><term>Article synthèse</term><term>Agoniste</term><term>Affinité</term><term>Traitement</term><term>Neurone</term><term>Mécanisme action</term><term>Structure secondaire</term><term>Sélectivité</term><term>Récepteur couplé protéine G</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide that was initially isolated from hypothalamus extracts on the basis of its ability to stimulate the production of cAMP in cultured pituitary cells. Recent studies have shown that PACAP exerts potent neuroprotective effects not only in vitro but also in in vivo models of Parkinson's disease, Huntington's disease, traumatic brain injury and stroke. The protective effects of PACAP are based on its capacity to prevent neuronal apoptosis by acting directly on neurons or indirectly through the release of neuroprotective factors by astrocytes. These biological activities are mainly mediated through activation of the PAC 1 receptor which is currently considered as a potential target for the treatment of neurodegenerative diseases. However, the use of native PACAP, the endogenous ligand of PAC1, as an efficient neuroprotective drug is actually limited by its rapid degradation. Moreover, injection of PACAP to human induces peripheral side effects which are mainly mediated through VPAC I and VPAC2 receptors. Strategies to overcome these compromising conditions include the development of metabolically stable analogs of PACAP acting as selective agonists of the PAC1 receptor. This review presents an overview of the structure-activity relationships of PACAP and summarizes the molecular and conformational requirements for activation of PAC1 receptor. The applicability of PACAP analogs as therapeutic agents for treatment of neurodegenerative diseases is also discussed.</div></front></TEI><affiliations><list><country><li>Canada</li><li>France</li></country><region><li>Haute-Normandie</li><li>Région Normandie</li></region><settlement><li>Rouen</li></settlement><orgName><li>Université de Rouen</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Bourgault, S" sort="Bourgault, S" uniqKey="Bourgault S" first="S." last="Bourgault">S. Bourgault</name></noRegion><name sortKey="Dejda, A" sort="Dejda, A" uniqKey="Dejda A" first="A." last="Dejda">A. Dejda</name><name sortKey="Doan, N D" sort="Doan, N D" uniqKey="Doan N" first="N. D." last="Doan">N. D. Doan</name><name sortKey="Fournier, A" sort="Fournier, A" uniqKey="Fournier A" first="A." last="Fournier">A. Fournier</name></country><country name="France"><region name="Région Normandie"><name sortKey="Bourgault, S" sort="Bourgault, S" uniqKey="Bourgault S" first="S." last="Bourgault">S. Bourgault</name></region><name sortKey="Bourgault, S" sort="Bourgault, S" uniqKey="Bourgault S" first="S." last="Bourgault">S. Bourgault</name><name sortKey="Dejda, A" sort="Dejda, A" uniqKey="Dejda A" first="A." last="Dejda">A. Dejda</name><name sortKey="Doan, N D" sort="Doan, N D" uniqKey="Doan N" first="N. D." last="Doan">N. D. Doan</name><name sortKey="Fournier, A" sort="Fournier, A" uniqKey="Fournier A" first="A." last="Fournier">A. Fournier</name><name sortKey="Vaudry, D" sort="Vaudry, D" uniqKey="Vaudry D" first="D." last="Vaudry">D. Vaudry</name><name sortKey="Vaudry, D" sort="Vaudry, D" uniqKey="Vaudry D" first="D." last="Vaudry">D. Vaudry</name><name sortKey="Vaudry, H" sort="Vaudry, H" uniqKey="Vaudry H" first="H." last="Vaudry">H. Vaudry</name><name sortKey="Vaudry, H" sort="Vaudry, H" uniqKey="Vaudry H" first="H." last="Vaudry">H. Vaudry</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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