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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/181542
Cationic Carbosilane Dendrimers Prevent Abnormal α-Synuclein Accumulation in Parkinson's Disease Patient-Specific Dopamine Neurons
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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.
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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 CHAMORRO, Ángel. Cationic Carbosilane Dendrimers Prevent Abnormal α-Synuclein Accumulation in Parkinson's Disease Patient-Specific Dopamine Neurons. _Biomacromolecules_. 2021. Vol. 22, núm. 11, pàgs. 4582-4591. [consulta: 25 de febrer de 2026]. ISSN: 1525-7797. [Disponible a: https://hdl.handle.net/2445/181542]