Investigating the Impact of a Mutation Associated with Amyotrophic Lateral Sclerosis on Annexin A11 Protein

• Grant number: 23/10418-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2023
• End date: June 30, 2024
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Luis Felipe Santos Mendes
• Grantee: Rodrigo Jose Silva Sena
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Annexins, proteins that bind to phospholipids in a calcium-dependent manner, are essential for the health and homeostasis of the organism, given their participation in various biological processes, such as anticoagulation, cell signaling, cell growth regulation, apoptosis, inflammation, vesicle fusion, and intracellular transport. In this project, our focus will be on Annexin A11 (AnxA11), a crucial member of the annexin family. AnxA11 is associated with various medical conditions, including systemic autoimmune diseases and sarcoidosis. Moreover, alterations in this protein have been linked to the development of various types of cancer, resistance to chemotherapy, and tumor recurrence. Recently, it was discovered that the D40G genetic mutation in AnxA11 is often found in patients with Amyotrophic Lateral Sclerosis (ALS). This mutant protein forms intracellular aggregates and interferes with the pattern of protein interaction with its molecular partners. In this innovative project, we will analyze how this mutation affects the biophysical and biochemical properties of AnxA11. Our goal is to better understand the development of the pathology caused by this hereditary mutation, as well as to identify the characteristics of the aggregates formed by it. With this information, we hope to pave the way for the search for future therapeutic strategies.