INVESTIGADORES
AVILA Cesar Luis
congresos y reuniones científicas
Título:
PAMAM dendrimers of generation 4.5 and its complexes with curcumin prevent the α-synuclein aggregation
Autor/es:
IGARTUA, DE; GONZALEZ-LIZARRAGA, MF; MARTINEZ, CS; AVILA, CL; CHEHIN, R; CHIARAMONI, NS; PRIETO, MJ
Reunión:
Jornada; Jornadas Virtuales de la SAB; 2020
Resumen:
Parkinson´s disease (PD) is a neurodegenerative disease characterized by α-synuclein aggregation in dopaminergic neurons, increased levels of oxidative stress, and neuroinflammation. To date, there is no pharmacological treatment to stop the progression of the disease. For this reason, it is imperative to develop disease-modifying therapies that prevent or delay disease progression. Furthermore, due to the multifactorial characteristics of PD, these treatments must be multitarget and effective both against α-synuclein aggregation, as well as against oxidative stress and neuroinflammation.Curcumin (CUR) is a natural polyphenol that could modulate the PD progression since its antioxidant and anti-inflammatory properties might reduce the levels of oxidative stress and neuroinflammation. However, clinical studies did not have positive results, which could be due to CUR insolubility in aqueous solutions, short half-life, and low bioavailability. For these, CUR is a good candidate to be used in nanocarriers. Dendrimers are used as nanocarriers due to the possibility of encapsulating drug molecules in their interior or anchoring drug molecules to their surface groups. Moreover, it has been recently shown that dendrimers could have intrinsic activity and act as nanodrugs per se, exhibiting anti-protein aggregation, anti-viral, anti-bacterial, and anti-inflammatory properties.Using a combination of biophysical techniques together with in vitro and in vivo models, we demonstrated: (i) the dendrimer DG4.5 increase the solubility and stability of CUR forming DG4.5-CUR complexes; (ii) the DG4.5-CUR complexes result biocompatible in vitro; and (iii) both the DG4.5 and DG4.5-CUR complexes impact on the α-synuclein aggregation. In conclusion, this work proposes the use of dendrimers as nanodrugs capable of inhibiting α-synuclein aggregation. Furthermore, this work proposes the incorporation of curcumin into dendrimers as a drug capable of reducing oxidative stress and neuroinflammation.Acknowldegments UNQ, IMMCA, CONICET