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Meridianins Rescue Cognitive Deficits, Spine Density and Neuroinflammation in the 5xFAD Model of Alzheimer's Disease.
Rodríguez-Urgellés, Ened; Sancho-Balsells, Anna; Chen, Wanqi; López-Molina, Laura; Ballasch, Ivan; Del Castillo, Ignacio; Avila, Conxita; Alberch, Jordi; Giralt, Albert.
Afiliación
  • Rodríguez-Urgellés E; Departament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
  • Sancho-Balsells A; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Chen W; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
  • López-Molina L; Departament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
  • Ballasch I; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Del Castillo I; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
  • Avila C; Departament de Biomedicina, Facultat de Medicina, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain.
  • Alberch J; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
  • Giralt A; Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Front Pharmacol ; 13: 791666, 2022.
Article en En | MEDLINE | ID: mdl-35281935
Glycogen synthase kinase 3ß (GSK3ß) is a core protein, with a relevant role in many neurodegenerative disorders including Alzheimer's disease. The enzyme has been largely studied as a potential therapeutic target for several neurological diseases. Unfortunately, preclinical and clinical studies with several GSK3ß inhibitors have failed due to many reasons such as excessive toxicity or lack of effects in human subjects. We previously reported that meridianins are potent GSK3ß inhibitors without altering neuronal viability. In the present work, we examine whether meridianins are capable to inhibit neural GSK3ß in vivo and if such inhibition induces improvements in the 5xFAD mouse model of Alzheimer's Disease. Direct administration of meridianins in the third ventricle of 5xFAD mice induced robust improvements of recognition memory and cognitive flexibility as well as a rescue of the synaptic loss and an amelioration of neuroinflammatory processes. In summary, our study points out meridianins as a potential compound to treat neurodegenerative disorders associated with an hyperactivation of GSK3ß such as Alzheimer's disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Front Pharmacol Año: 2022 Tipo del documento: Article País de afiliación: España Pais de publicación: Suiza