Investigation of proteasome dynamics in Alzheimer's disease

• Grant number: 25/25984-0
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: April 18, 2026
• End date: June 06, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Sérgio Teixeira Ferreira
• Grantee: Augusto Batista Farias
• Host Institution: Instituto de Biofísica Carlos Chagas Filho (IBCCF). Universidade Federal do Rio de Janeiro (UFRJ)

Abstract

This project aims to investigate how the dynamics of the proteasome, the main cellular degradation machinery, is affected in Alzheimer's disease (AD). Data from our group indicate that Abeta oligomers (AbOs), neurotoxins associated with AD, inhibit brain proteasome activity and induce changes in proteasome subcellular localization in neurons. However, it is not yet established whether AbOs alter proteasome assembly and whether proteasome adaptor proteins are involved in these AbO-induced changes. In this work, we will: (1) investigate whether AbOs induce changes in brain proteasome assembly, and (2) evaluate whether knockdown of the proteasome adaptor protein ECM29 alters proteasome activity, localization, and composition in experimental models of AD. (AU)