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http://hdl.handle.net/2445/181542
Title: | Cationic Carbosilane Dendrimers Prevent Abnormal α-Synuclein Accumulation in Parkinson's Disease Patient-Specific Dopamine Neurons |
Author: | Ferrer Lorente, Raquel Lozano Cruz, Tania Fernández Carasa, Irene Miłowska, Katarzyna Mata, Francisco Javier de la Bryszewska, Maria Consiglio, Antonella Ortega, Paula Gómez, Rafael Raya, Angel |
Keywords: | Malaltia de Parkinson Dopamina Parkinson's disease Dopamine |
Issue Date: | 6-Oct-2021 |
Publisher: | American Chemical Society |
Abstract: | Accumulation of misfolded α-synuclein (α-syn) is a hallmark of Parkinson's disease (PD) thought to play important roles in the pathophysiology of the disease. Dendritic systems, able to modulate the folding of proteins, have emerged as promising new therapeutic strategies for PD treatment. Dendrimers have been shown to be effective at inhibiting α-syn aggregation in cell-free systems and in cell lines. Here, we set out to investigate the effects of dendrimers on endogenous α-syn accumulation in disease-relevant cell types from PD patients. For this purpose, we chose cationic carbosilane dendrimers of bow-tie topology based on their performance at inhibiting α-syn aggregation in vitro. Dopamine neurons were differentiated from induced pluripotent stem cell (iPSC) lines generated from PD patients carrying the LRRK2G2019S mutation, which reportedly display abnormal accumulation of α-syn, and from healthy individuals as controls. Treatment of PD dopamine neurons with non-cytotoxic concentrations of dendrimers was effective at preventing abnormal accumulation and aggregation of α-syn. Our results in a genuinely human experimental model of PD highlight the therapeutic potential of dendritic systems and open the way to developing safe and efficient therapies for delaying or even halting PD progression. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1021/acs.biomac.1c00884 |
It is part of: | Biomacromolecules, 2021, vol. 22, num. 11, p. 4582-4591 |
URI: | http://hdl.handle.net/2445/181542 |
Related resource: | https://doi.org/10.1021/acs.biomac.1c00884 |
ISSN: | 1525-7797 |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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