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

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7609-7621
Number of pages13
JournalChemistry - A European Journal
Volume26
Issue number34
DOIs
Publication statusAccepted/In press - 1 Jan 2020

Keywords

  • anti-amyloid agents
  • dendrimers
  • diabetes
  • peptides
  • protein structures

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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