Science and Technology Production
Congress
Authorship
Delgado Ocaña, Susana
;
Gonzalez, Nazareno
;
Gentile, Iñaki
;
GARRO, HUGO ALEJANDRO
;
Schibich, Daniela
;
Maria E. Chesta
;
Menacho Márquez, Mauricio
;
Fernández, Claudio O.
Date
2018
Publishing House and Editing Place
Sociedad Argentina de Investigación en Neurociencias
Summary
Information provided by the agent in
SIGEVA
Amyloid aggregation of alpha-synuclein (αS) in Parkinson?s disease (PD) results in cellular toxicityand neuronal death. Several mutations in αS gene are associated with familial PD, supporting acentral role for the protein in the development of the disease. However, the precise contributionof αS aggregates to neuronal impairment and death is not well understood. Previous work in ourlab demonstrated that aromatic side chains of the N-terminal tyrosine residue at position 39 (Y3...
Amyloid aggregation of alpha-synuclein (αS) in Parkinson?s disease (PD) results in cellular toxicityand neuronal death. Several mutations in αS gene are associated with familial PD, supporting acentral role for the protein in the development of the disease. However, the precise contributionof αS aggregates to neuronal impairment and death is not well understood. Previous work in ourlab 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 Y39residue 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 replacementof 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 opennew perspectives to elucidate the molecular basis behind the amyloid aggregation of the proteinαS.
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Key Words
structural and cell biology strategiesParkinson?s diseasealpha-synucleinAmyloid aggregation