Cintia Roodveldt
University of Seville, Spain
Title: Vaccination with heat-shock protein-chaperoned ï¡-synuclein as a novel immunotherapeutic strategy against Parkinsons Disease
Biography
Biography: Cintia Roodveldt
Abstract
ï¡-synuclein (ï¡Syn) is an amyloid-forming protein whose aggregation is linked to Parkinson’s disease (PD), a ‘misfolding’ neurodegenerative disorder. ï¡Synï€ has also been found to play a critical role in the immune imbalance accompanying disease progression, a feature that has prompted research on the immunological role of ï¡Syn in PD as well as the search for an effective ï¡Syn-based immunotherapy. In this work, we investigated a novel approach that simultaneously exploits two important features of certain heat-shock proteins (HSPs): their classical ‘chaperone’ activities and their recently discovered and diverse ‘immunoactive’ properties. In particular, we have characterized the immune response elicited by immunization of naïve C57BL/6 mice with a ï¡Syn/HSP protein combination. Our results show specific differences in mice immunized with the ï¡Syn/HSP complex when compared to controls, including their Treg (CD4+CD25+Foxp3+) and Teff (CD4+Foxp3-) cell contents, altered antigen-specific response of isolated splenocytes, and different anti-ï¡Syn antibody levels in blood. Moreover, the measured serum levels of IFN-ï§ and IL-10 cytokines indicated a unique shift towards a Th2 immunomodulatory/ immunoprotective phenotype in mice immunized with ï¡Syn/HSP. Finally, we have tested the therapeutic potential of the ï¡Syn/HSP vaccine in a 1.methyl-4.phenyl-1,2,3,6-tetrahydropyridine (MPTP) PD mouse model, showing improvements of PD symptoms in treated mice, according to standard behavioral tests (e.g. limb stride variation, rearing). Overall, we propose the use of functional ‘HSP-chaperoned amyloid/aggregating proteins’ generated with appropriate HSP-client protein combinations, such as the ï¡Syn/HSP complex used in this study, as a novel strategy for immune-based intervention against synucleinopathies and other amyloid or ‘misfolding’ neurodegenerative disorders.