Chaperones machines to combat protein aggregation in Parkinson's Disease

• Grant number: 17/24722-6
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: March 01, 2018
• End date: August 31, 2018
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Merari de Fátima Ramires Ferrari
• Grantee: Raquel de Souza Lima
• Supervisor: Harm Harmannus Kampinga
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University Medical Center Groningen (UMCG), Netherlands
• Associated to the scholarship: 16/04409-9 - Analysis of autophagy and the role of co-chaperone bag-2 upon protein aggregates in neurodegenerative diseases, BP.MS

Abstract

Aging is a worldwide issue and the understanding of the cellular events associated to this process are important for the study of age-related diseases, like in neurodegenerative disorders such as Alzheimer's (AD) and Parkinson's diseases (PD). Most cases of PD are sporadic and the small fraction of PD cases which are familial implicates genetic susceptibility, such as point mutations, duplication or triplication in alpha-synuclein gene (SNCA) and mutations in other genes. It is thought that the accumulation of alpha-synuclein and consequently aggregation is due to deficits in the protein degradation. The degradation of alpha-synuclein can occur by the ubiquitin-proteasome system (UPS) or by autophagy, pathways that are important for protein quality control and cellular homeostasis. The initial regulation of protein quality control is mediated by molecular chaperones, such as Hsp70, DNAJs and proteins of BAG family, like BAG-2. They act to facilitate protein folding, protein transport over membranes, protein remodeling, protein disaggregation, refolding or degradation. In view of this, it is proposed to evaluate the putative connections, if exist, between BAG2, and DNAJB6/DNAJB2 and how they regulate Hsp70 machines to degrade alpha-synuclein. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LIMA, RAQUEL S.; CARRETTIERO, DANIEL C.; FERRARI, MERARI F. R.. BAG2 prevents Tau hyperphosphorylation and increases p62/SQSTM1 in cell models of neurodegeneration. MOLECULAR BIOLOGY REPORTS, v. N/A, p. 13-pg., 2022-05-25. (11/06434-7, 13/08028-1, 18/07592-4, 17/24722-6, 16/04409-9)