A-T cerebellar neurodegeneration and inositol phosphate signalling

Research Project information

Principal researcher: Professor Tanya Paull
Institute: The University of Texas at Austin, USA
Cost: £90,074 over 12 months in partnership with the A-T Society (UK), AEFAT (Spain) and BrAshA-T (Australia)
Start Date: 1st of June 2021

What are the researchers proposing to do?
This project builds on work that has already been carried out by Professor Paull.  Previous research in her lab looked at cerebellum and neocortex brain tissue from A-T patients and matched controls that showed marked differences in protein aggregation* in A-T cerebellum as well as the overall loss of specific proteins involved in calcium signalling. This pathway of calcium signalling is already known to be disrupted in familial forms of another form of ataxia, spinocerebellar ataxia.

* protein aggregation – when disordered proteins or mis-folded proteins accumulate and clump together. Protein aggregation has been implicated in a wide variety of neurodegenerative conditions.

Why?
Even though researchers know a great deal about the ATM protein and what it does in a wide range of organisms, they have not come closer to addressing the primary debilitating aspect of A-T,  “the neurodegeneration”.  It has become clear to the team that there has been relatively little analyses of actual human A-T patient brain tissue, which they believe holds the key to understanding the brain-specific aspects of A-T.

How will the research be done?
Professor Paull will further investigate the changes in protein levels in A-T brain tissue by determining if these arise from changes in gene expression.  She will also use a human neuronal system to determine if calcium signalling proteins are regulated by ATM or its activity. Her work is aimed at increasing our understanding of the cause/s of protein abnormalities that have been observed in A-T brain tissues.

How could it make a difference to the lives of those affected by A-T?
Ultimately, only by understanding why neurodegeneration occurs in A-T will researchers be able to start the development of potential treatments.  Treatment strategies targeting neurodegeneration would make a huge impact on the quality of life of those living with A-T.