Cationic Carbosilane Dendritic Systems as Promising Anti-Amyloid Agents in Type 2 Diabetes

Tania Lozano-Cruz, Gema Alcarraz-Vizán, F. Javier de la Mata, Sara de Pablo, Paula Ortega, Yorley Duarte, Felipe Bravo-Moraga, Fernando D. González-Nilo, Anna Novials, Rafael Gómez

Resultado de la investigación: Contribución a una revistaArtículo

Resumen

The most common denominator of many of the neurodegenerative diseases is badly folded protein accumulation, which results in the formation of insoluble protein deposits located in different parts of the organism, causing cell death and tissue degeneration. Dendritic systems have turned out to be a promising new therapeutic approach for the treatment of these diseases due to their ability to modulate the folding of these proteins. With this perspective, and focused on type 2 diabetes (T2D), characterized by the presence of deposits containing the amyloidogenic islet amyloid polypeptide (IAPP), we demonstrate how different topologies of cationic carbosilane dendrimers inhibit the formation of insoluble protein deposits in pancreatic islets isolated from transgenic Tg-hIAPP mice. Also, the results obtained by the modification of dendritic carbosilane wedges with the chemical chaperone 4-phenylbutyric acid (4-PBA) at the focal point confirmed their potential as anti-amyloid agents with a concentration efficiency in their therapeutic action five orders of magnitude lower than that observed for free 4-PBA. Computational studies, which determined the main interaction between IAPP and dendrimers at the atomic level, support the experimental work.

Idioma originalInglés
PublicaciónChemistry - A European Journal
DOI
EstadoEn prensa - 1 ene 2020

Áreas temáticas de ASJC Scopus

  • Catálisis
  • Química orgánica

Huella Profundice en los temas de investigación de 'Cationic Carbosilane Dendritic Systems as Promising Anti-Amyloid Agents in Type 2 Diabetes'. En conjunto forman una huella única.

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    Lozano-Cruz, T., Alcarraz-Vizán, G., de la Mata, F. J., de Pablo, S., Ortega, P., Duarte, Y., Bravo-Moraga, F., González-Nilo, F. D., Novials, A., & Gómez, R. (Aceptado/En prensa). Cationic Carbosilane Dendritic Systems as Promising Anti-Amyloid Agents in Type 2 Diabetes. Chemistry - A European Journal. https://doi.org/10.1002/chem.202000091