Cationic Carbosilane Dendritic Systems as Promising Anti‐Amyloid Agents in Type 2 Diabetes
| Autor: | Tania Lozano-Cruz, Paula Ortega, F. Javier de la Mata, Felipe Bravo-Moraga, Sara de Pablo, Rafael Gómez, Yorley Duarte, Fernando D. González-Nilo, Gema Alcarraz-Vizán, Anna Novials |
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| Rok vydání: | 2020 |
| Předmět: |
Programmed cell death
Amyloid Transgene Mice Transgenic 010402 general chemistry 01 natural sciences Catalysis Islets of Langerhans Mice Protein structure Dendrimer medicine Animals Humans geography geography.geographical_feature_category 010405 organic chemistry Chemistry Pancreatic islets Organic Chemistry Amyloidosis General Chemistry Silanes Islet Phenylbutyrates Islet Amyloid Polypeptide 0104 chemical sciences medicine.anatomical_structure Diabetes Mellitus Type 2 Biophysics Chemical chaperone |
| Zdroj: | Chemistry – A European Journal. 26:7609-7621 |
| ISSN: | 1521-3765 0947-6539 |
| DOI: | 10.1002/chem.202000091 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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