In:
Chemistry – A European Journal, Wiley, Vol. 26, No. 34 ( 2020-06-18), p. 7609-7621
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0947-6539
,
1521-3765
DOI:
10.1002/chem.202000091
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2020
ZDB Id:
1478547-X
