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Characterization of posttranslational modifications that modulate DNAJB1, a targeting factor of the human Hsp70-based protein disaggregase

Grant number: 22/03729-0
Support Opportunities:Regular Research Grants
Duration: November 01, 2022 - October 31, 2025
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Convênio/Acordo: Monash University
Principal Investigator:Carlos Henrique Inacio Ramos
Grantee:Carlos Henrique Inacio Ramos
Principal researcher abroad: Nadinath B Nillegoda
Institution abroad: Monash University, Australia
Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:17/26131-5 - The chaperome: study of the relationship of the structure of its components and the maintenance of proteostasis, AP.TEM
Associated scholarship(s):23/06727-1 - Technical assistance to the FAPESP-MONASH Cooperation Project, BP.TT

Abstract

Amyloid-type protein aggregation is a common feature of many neuro/neuromuscular degenerative disorders such as Huntington's disease (HD). Although these diseases show distinct clinical features, at the molecular level, protein aggregation modulates disease progression by a gain-of-toxicity mechanism(s). Recent epidemiological studies by the World Health Organization revealed that >55 million people worldwide are living with such conditions. DNAJB1 targeting factor-containing Hsp70-based protein disaggregases in humans were recently shown to efficiently disassemble amyloid-type aggregates and counteract the associated toxicities, thus showcasing the immense therapeutic value of boosting this activity in cells. The proposed project presents an innovative research program to establish how posttranslational modifications (PTMs) regulate DNAJB1 in amyloid disaggregation function. (AU)

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