KEY WORDS: neurodegenerative disease, SCA3, spinocerebellar ataxia 3, ataxin-3, ATXN3, SCA3 mouse, knock-in, mutant protein, PolyQ, CAG repeats, autophagy, proteasome
Research topic: Investigation of a new therapeutic strategy to lower mutant protein in SCA3 / MJD
Principal Investigator: Maciej Figiel
I. Project description
Neurodegenerative diseases, including polyglutamine diseases and Alzheimer's disease, are currently incurable. A model disease in this group is spinocerebellar ataxia type 3 (SCA3), which is a genetic neurodegenerative disease caused by a particular type of mutation that results in an increased number of CAG nucleotide repeats in the ATXN3 gene sequence. The mutation in the ATXN3 gene results in the defective protein ataxin-3, which forms toxic aggregates in the cell and also increases the cellular level of beta-amyloid. Ataxin-3 plays a crucial role in controlling which proteins and organelles should be cleared in the cell through two related cellular mechanisms called autophagy and UPS. Ataxin-3 recognizes a protein tag called ubiquitin that directs a protein or cell fragment for breakdown, and detaches this tag from the protein, thereby preventing premature removal of the proteins from the cell. In this project, we will investigate whether forcing the controlled removal of cell fragments by small molecule drugs will repair the disrupted cellular processes resulting from the ATXN3 mutation.
We hope that thanks to this project, we will learn more about the specific role of one of the key pathogenic processes in neurodegenerative diseases related to the dysfunction of protein clearance mechanisms. A detailed study of this mechanism will provide a better understanding of SCA3 and other neurodegenerative diseases, which will enable the design of appropriate treatments.
Ph D Candidate: Development Of An Innovative Therapy For Arteriovenous Fistula Failure, Maastricht University, Netherlands, about 7 hours ago
PhD candidate: Development of an innovative therapy for arteriovenous fistula failure PhD candidate: Development of an innovative therapy for arteriovenous fistula failure Published Deadline Locat...
Ph D Candidate (1.0 Fte) At The School For Cardiovascular Diseases, Department Of Cardiology, Maastricht University, Netherlands, 8 days ago
PhD candidate (1.0 FTE) at the School for Cardiovascular Diseases, department of Cardiology PhD candidate (1.0 FTE) at the School for Cardiovascular Diseases, department of Cardiology Published De...
Ph D Position In Bioinformatics , University of Southern Denmark, Denmark, 5 days ago
The Institute of Molecular Medicine (IMM) at SDU PhD position in Bioinformatics Institute of Molecular Medicine (IMM) aims to generate new knowledge on the function of the human body and disease m...
Ph D Candidate On M Rna Trafficking And Local Translation At The Synapse, Vrije Universiteit Amsterdam, Netherlands, about 9 hours ago
Do you want to pursue a PhD in cellular neuroscience? Please apply at Vrije Universiteit Amsterdam (VU). Location: AMSTERDAM FTE: 1 Job description You will be working as a PhD candidate on "mRNA...
Ph D Position: Biophysics & Neuroscience, Delft University of Technology, Netherlands, about 14 hours ago
How do neurons form networks at the nanoscale? Are you interested in identifying underlying molecular mechanisms of synapse formation? A 4-year position is available for a PhD candidate in the res...
Ph D Student In Quantitative Biology (Pa2023/216) , University of Lund, Sweden, 1 day ago
Description of the workplace The research group of Clinical Memory Research focuses on defining and understanding biological processes in Alzheimer’s disease and other neurodegenerative diseases. ...