Transcript
[Beginning of recorded material]
[Title card animation: Dementia Australia Research Foundation - Prevent]
Dr Kristie Stefanoska: My name is Kristie Stefanoska. I'm a research fellow in dementia at Flinders University. So, dementia is an umbrella term that's used to describe a group of neurodegenerative diseases that cause memory loss, and one of the most common forms of dementia is Alzheimer's disease.
I was always really fascinated with the brain, and during my undergraduate, we had a family member diagnosed with dementia. And we saw, firsthand, the impact that this had on them, as well as us as a family. And right then, I knew that I really wanted to be a part of, I guess, solving the question of what is causing dementia, and I decided to do a PhD and become a neuroscientist.
Basic science is so important, and often, this is where major discoveries are made. And if we're to put an end to Alzheimer's disease, we need to first understand the basic events or the molecular events that are causing dementia.
So, we previously made the discovery that tau, this protein that's implicated in Alzheimer's disease, interacts with another protein called NSF in brain cells. NSF plays a vital role in brain cells to help them communicate effectively. So, you can think of brain cells as little factories that send and receive messages, and NSF plays an important role to allow the messages to be delivered effectively, and the way that it does this is through trafficking vesicles. So, you can imagine vesicles in the brain as little courier trucks that contain packages, and these packages contain messages. And what it does is it ensures that the courier trucks, or the vesicles, are trafficked to the right location, and that they empty their contents at the appropriate time.
Another important function of NSF is to regulate the stability of an AMPA receptor - so this can be thought of as an antenna on brain cells that receive signals, and this is an important process in learning and memory. And what we found, previously, was the higher the levels of tau, this reduced NSF activity, and therefore, changed it distribution within brain cells.
With the project that's funded by Bondi2Barossa and Dementia Australia Research Foundation, we're now able to look at the interaction between these two brain proteins, to understand how they contribute to tau-mediated dementia. In other words, what we are also trying to establish is whether restoring NSF activity, so this brain protein that can be thought of as a postal worker in the brain, whether it can prevent cognitive deficits, and protect against a form of cell death in the brain that leads to dementia.
This project is a team effort, and PhD student Emmanuel Prikas will be working on the different aspects of the project. So in aim one, trying to optimise NSF activities, so by increasing NSF activity, can we prevent the cognitive deficits in our Alzheimer's disease mice that have been genetically engineered to have dementia?
Emmanuel: So, there are two aspects to this project - there's an in vivo component, which involves Alzheimer's disease modelled mice going through a battery of memory tests, and we're assessing their performance in these memory tests. And the second component of the project is in vitro based, which involves manipulating brain cells in dishes. The hope is to find a link between different forms of tau, this memory associated protein, NSF, and how these two proteins may or may not contribute to a very specific form of cell death that we see in dementia patient tissue.
Dr Kristie Stefanoska: In the final aim, we are looking at whether changes in the tau protein, on specific spots known as p-tau contribute to this NSF interaction and reduction in NSF activity, that leads to the cognitive deficits. It's my belief that through understanding these steps, whether we can optimise NSF activity, how does this interaction cause brain cell death, and is it because of specific changes on the tau, we're better able to not only understand what may be causing dementia, but also to devise therapeutic strategies to potentially slow down the progression, means a great deal to me.
[Title card]
This research is supported by:
Bondi2Barossa Project Grant
Dementia Australia Research Foundation
Flinders University
Dr Stefanoska would like to acknowledge the research team:
Dr Arne Itter, Emmanuel Prikas and everyone in the Molecular Memory and Dementia Research Lab.
We thank Bondi2Barossa for its support.
[End title card]
[Title card]
Dementia Australia Research Foundation:
A cure is just the beginning
If you would like to see dementia research make real impact, donate today:
1300 636 679
www.dementia.org.au/donate-research
[End title card]
[END of recorded material]
