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Auteur Cristina M. ALBERINI |
Documents disponibles écrits par cet auteur (1)
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CIM6P/IGF-2 Receptor Ligands Reverse Deficits in Angelman Syndrome Model Mice / Emmanuel CRUZ in Autism Research, 14-1 (January 2021)
[article]
Titre : CIM6P/IGF-2 Receptor Ligands Reverse Deficits in Angelman Syndrome Model Mice Type de document : Texte imprimé et/ou numérique Auteurs : Emmanuel CRUZ, Auteur ; Giannina DESCALZI, Auteur ; Adam STEINMETZ, Auteur ; Helen E. SCHARFMAN, Auteur ; Aaron KATZMAN, Auteur ; Cristina M. ALBERINI, Auteur Article en page(s) : p.29-45 Langues : Anglais (eng) Mots-clés : Angelman syndrome Ube3a audiogenic seizure cation-independent mannose-6-phosphate receptor insulin-like growth factor 2 insulin-like growth factor 2 receptor mannose-6-phosphate memory motor response mouse model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS), a genetic disorder that primarily affects the nervous system, is characterized by delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy). No existing therapies are capable of comprehensively treating the deficits in AS; hence, there is an urgent need to identify new treatments. Here we show that insulin-like growth factor 2 (IGF-2) and mannose-6-phosphate (M6P), ligands of two independent binding sites of the cation-independent M6P/IGF-2 receptor (CIM6P/IGF-2R), reverse most major deficits of AS modeled in mice. Subcutaneous injection of IGF-2 or M6P in mice modeling AS restored cognitive impairments as assessed by measurements of contextual and recognition memories, motor deficits assessed by rotarod and hindlimb clasping, and working memory/flexibility measured by Y-maze. IGF-2 also corrected deficits in marble burying and significantly attenuated acoustically induced seizures. An observational battery of tests confirmed that neither ligand changed basic functions including physical characteristics, general behavioral responses, and sensory reflexes, indicating that they are relatively safe. Our data provide strong preclinical evidence that targeting CIM6P/IGF-2R is a promising approach for developing novel therapeutics for AS. LAY SUMMARY: There is no effective treatment for the neurodevelopmental disorder Angelman syndrome (AS). Using a validated AS mouse model, the Ube3a(m-/p+) , in this study we show that systemic administration of ligands of the cation independent mannose-6-phosphate receptor, also known as insulin-like growth factor 2 receptor (CIM6P/IGF-2R) reverses cognitive impairment, motor deficits, as well as seizures associated with AS. Thus, ligands that activate the CIM6P/IGF-2R may represent novel, potential therapeutic targets for AS. En ligne : http://dx.doi.org/10.1002/aur.2418 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441
in Autism Research > 14-1 (January 2021) . - p.29-45[article] CIM6P/IGF-2 Receptor Ligands Reverse Deficits in Angelman Syndrome Model Mice [Texte imprimé et/ou numérique] / Emmanuel CRUZ, Auteur ; Giannina DESCALZI, Auteur ; Adam STEINMETZ, Auteur ; Helen E. SCHARFMAN, Auteur ; Aaron KATZMAN, Auteur ; Cristina M. ALBERINI, Auteur . - p.29-45.
Langues : Anglais (eng)
in Autism Research > 14-1 (January 2021) . - p.29-45
Mots-clés : Angelman syndrome Ube3a audiogenic seizure cation-independent mannose-6-phosphate receptor insulin-like growth factor 2 insulin-like growth factor 2 receptor mannose-6-phosphate memory motor response mouse model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS), a genetic disorder that primarily affects the nervous system, is characterized by delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy). No existing therapies are capable of comprehensively treating the deficits in AS; hence, there is an urgent need to identify new treatments. Here we show that insulin-like growth factor 2 (IGF-2) and mannose-6-phosphate (M6P), ligands of two independent binding sites of the cation-independent M6P/IGF-2 receptor (CIM6P/IGF-2R), reverse most major deficits of AS modeled in mice. Subcutaneous injection of IGF-2 or M6P in mice modeling AS restored cognitive impairments as assessed by measurements of contextual and recognition memories, motor deficits assessed by rotarod and hindlimb clasping, and working memory/flexibility measured by Y-maze. IGF-2 also corrected deficits in marble burying and significantly attenuated acoustically induced seizures. An observational battery of tests confirmed that neither ligand changed basic functions including physical characteristics, general behavioral responses, and sensory reflexes, indicating that they are relatively safe. Our data provide strong preclinical evidence that targeting CIM6P/IGF-2R is a promising approach for developing novel therapeutics for AS. LAY SUMMARY: There is no effective treatment for the neurodevelopmental disorder Angelman syndrome (AS). Using a validated AS mouse model, the Ube3a(m-/p+) , in this study we show that systemic administration of ligands of the cation independent mannose-6-phosphate receptor, also known as insulin-like growth factor 2 receptor (CIM6P/IGF-2R) reverses cognitive impairment, motor deficits, as well as seizures associated with AS. Thus, ligands that activate the CIM6P/IGF-2R may represent novel, potential therapeutic targets for AS. En ligne : http://dx.doi.org/10.1002/aur.2418 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441