Abstracts of the 2018 Meeting of ArgentineSociety for Research in Neurosciences

DELGADO OCAÑA, SUSANA; GONZALEZ, NAZARENO; FERNÁNDEZ, CLAUDIO O.

ASN Neuro

Portland Press Ltd.

Año: 2019 vol. 11

1759-0914

Amyloid aggregation of alpha-synuclein (αS) in Parkinson?s disease (PD) results in cellular toxicity and neuronal death. Several mutations in αS gene are associated with familial PD, supporting a central role for the protein in the development of the disease. However, the precise contribution of αS aggregates to neuronal impairment and death is not well understood. Previous work in our lab demonstrated that aromatic side chains of the N-terminal tyrosine residue at position 39 (Y39) of αS plays a critical role in its fibrillation pathway. In order to understand the key role of Y39 residue on αS aggregation and toxicity, we designed different point mutants of the protein. Through the combination of biophysics and cell-based assays, we demonstrated that replacement of Tyr by Ala or Leu at position 39 led to protein variants with different amyloidogenic potential. Interestingly, strong correlation was observed between the in vitro and in cell studies. Altogether, our data highlight the importance of combining structural and cell biology strategies and open new perspectives to elucidate the molecular basis behind the amyloid aggregation of the protein αS