Elucidating the molecular mechanisms of aggregation of functional amyloids formed by human Neuropeptide Y

• Grant number: 23/09930-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: July 31, 2024
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Luis Felipe Santos Mendes
• Grantee: Murilo de Oliveira Souza
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

The study of amyloid fibril formation is a fundamental area of research due to its association with various neurodegenerative diseases and the unique ability of several proteins to form these structures, even without shared sequence similarities. This project focuses on the study of the molecular mechanisms of functional amyloid formation, with a focus on neuropeptides like Neuropeptide Y. These hormones, which play a crucial role in modulating neuronal activity and regulating a variety of physiological processes, are stored and released in the form of amyloids in nerve cells. Despite the nefarious role of amyloid aggregates in the evolution of neurodegenerative diseases, they also perform essential biological functions, forming an emerging study area. With this project, we seek to elucidate the aggregation and disaggregation kinetics of a functional amyloid example and investigate the mechanisms that allow cells to control this process without generating pathogenic structures. We intend to address key issues such as the hypothesis of high stability of functional amyloids, their kinetic formation mechanism, and the presence or absence of polymorphisms. Understanding these processes could provide new perspectives for treating neurodegenerative diseases and expand our understanding of stress physiology and regulation of the nervous system.