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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Prolyl Endopeptidase-Like Facilitates the alpha-Synuclein Aggregation Seeding, and This Effect Is Reverted by Serine Peptidase Inhibitor PMSF

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Autor(es):
Santos, Gabriel S. [1] ; Oyadomari, William Y. [1] ; Carvalho, Elizangela A. [1] ; Torquato, Ricardo S. [2] ; Oliveira, Vitor [1]
Número total de Autores: 5
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Dept Biophis, Escola Paulista Med, BR-04039032 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Dept Biochem, Escola Paulista Med, BR-04039032 Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: BIOMOLECULES; v. 10, n. 6 JUN 2020.
Citações Web of Science: 0
Resumo

The aggregation of alpha-synuclein (alpha-Syn) is a characteristic of Parkinson's disease (PD). alpha-Syn oligomerization/aggregation is accelerated by the serine peptidase, prolyl oligopeptidase (POP). Factors that affect POP conformation, including most of its inhibitors and an impairing mutation in its active site, influence the acceleration of alpha-Syn aggregation resulting from the interaction of these proteins. It is noteworthy, however, that alpha-Syn is not cleaved by POP. Prolyl endopeptidase-like (PREPL) protein is structurally related to the serine peptidases belonging to the POP family. Based on the alpha-Syn-POP studies and knowing that PREPL may contribute to the regulation of synaptic vesicle exocytosis, when this protein can encounter alpha-Syn, we investigated the alpha-Syn-PREPL interaction. The binding of these two human proteins was observed with an apparent affinity constant of about 5.7 mu M and, as in the alpha-Syn assays with POP, the presence of PREPL accelerated the oligomerization/aggregation events, with no alpha-Syn cleavage. Furthermore, despite this lack of hydrolytic cleavage, the serine peptidase active site inhibitor phenylmethylsulfonyl fluoride (PMSF) abolished the enhancement of the alpha-Syn aggregation by PREPL. Therefore, given the attention to POP inhibitors as potential drugs to treat synucleinopathies, the present data point to PREPL as another potential target to be explored for this purpose. (AU)

Processo FAPESP: 18/09158-0 - Prolil oligopeptidase: estrutura-atividade e secreção
Beneficiário:Vitor Marcelo Silveira Bueno Brandão de Oliveira
Modalidade de apoio: Auxílio à Pesquisa - Regular