Molecular mechanisms associated with amyotrophic lateral sclerosis: VAPB and reticulophagy.

• Grant number: 25/16746-9
• Support Opportunities: Scholarships in Brazil - Master
• Start date: January 01, 2026
• End date: May 31, 2027
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Luis Eduardo Soares Netto
• Grantee: Júlia Maria de Almeida Silvino
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

VAPs are membrane proteins that anchor to the endoplasmic reticulum (ER) and are present in all Eukaryotes. In mammals, these proteins are constitutively expressed and are encoded by two homologous genes: VAPA and VAPB. A mutation in the VAPB protein has been identified in individuals from a family affected by amyotrophic lateral sclerosis type 8 (ALS8). This mutation, located at codon 56 of this gene, results in the substitution of a highly conserved proline residue with a serine (P56S). This event results in the structural and functional impairment of VAPB, making it insoluble, and appears to be directly associated with the onset and progression of ALS8. In this context, the present project aims to investigate the role of reticulophagy in the cellular response to the accumulation of cytosolic protein aggregates of VAPB under the P56S mutation. The Saccharomyces cerevisiae model will be used, taking advantage of the availability of various tools that have already enabled us to obtain preliminary results. (AU)