Tools for Studying the Importance of alpha-Synuclein s Post-Translational Modifications in Parkinson s disease

ANTONELLA LEON; BETINA CORSICO; GIAN FRANCO CAVAZZUTTI; THOMAS M. JOVIN; EZEQUIEL GIMENEZ; AGUSTIN DE GANZO; LISANDRO J. FALOMIR LOCKHART

Córdoba

Workshop; AvH Kolleg 2017 Córdoba; 2017

Alexander Von Humboldt club Argentina

Protein aggregation is common in neurodegenerative diseases, presumably as a result of the combination of genetic predispositions and external factors, such as compounds that promote oxidative stress. In the case of Parkinson´s disease (PD), this condition leads to a gain of toxic function of the protein alpha-Synuclein (aSyn), even in the absence of genetic mutations in this protein. However, the identity of the toxic species remains elusive. In this sense, post-translational modifications (PTMs) are a well-known source of variability of proteins´ structure, function, and localization, and are therefore possible modulators of the physiopathology of aSyn in neurons.Our project aims for a better understanding of the triggering molecular events leading to PD and the development of innovative tools for the early diagnosis of the diseases commonly known as Synucleopathies. Our goals include the generation in vitro of different aSyn PTMs, and their characterization employing biophysical and biochemical methods. We will also analyze their influence on amyloid aggregation, membrane binding and cytotoxicity in neuron-like cell cultures. Finally, based on the results obtained, we plan to develop Nanobodies (VHHs) from llama that could recognize and quantitate specific aSyn PTMs as early biomarkers of Synucleopathies in complex biological samples.