Evaluation of 20S proteasome activators in preventing protein aggregate formation in a neurodegeneration cell model

• Grant number: 07/05620-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2007
• End date: November 30, 2008
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marilene Demasi
• Grantee: Francisco Humberto Dal Vechio Filho
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Present proposal is part of the project upon the Screening for Modulators of the 20S Proteasome (BioProspecta; Proc FAPESP: 06/06969-0; Coordenação: Dra. Marilene Demasi, Laboratório de Bioquímica e Biofísica - Instituto Butantan). Among the modulators isolated thus far, one of them refers to a catalytic activator of the 20S proteasome named Tnp1. Preliminary studies with that peptide showed that Tnp1 was able to activate the 20S proteasome either in vitro or inside cells and to decrease the pool of oxidized proteins from cells submitted to moderate oxidative challenge. In the present work, the main goal is to evaluate the effect of Tnp1 in a neurodegenerative cellular model (Amyotrophic Lateral Sclerosis) in order to address Tnp1 effect upon the prevention of protein aggregation.