Pre-clinical targets for vascular dementia treatment (PhD Studentship)

See glossary at bottom of page for definition of underlined words.

Summary

Vascular dementia is caused by a lack of blood supply to white matter regions of the brain. This lack of blood supply is thought to be caused by a class of proteins known as glutamate receptors. In this project, a series of drugs known to target glutamate receptors are tested for their ability to treat the neurodegenerative effects of VaD. The effects of these drugs are will be tested using a state-of-the-art model for VaD developed by this research group. This work will build upon what is known about white matter damage in dementia and pave the way for development of effective treatments.

What do we already know?

Dementia research has typically focussed on the changes to grey matter in the brain. More than half of the human brain consists of white matter which is considered the ‘internet’ of the brain responsible for wiring neurones together. Vascular dementia (VaD) is caused by the lack of blood supply to the white matter regions of the brain. This lack of blood supply is caused by a class of proteins known as glutamate receptors. This project seeks to utilise a model for VaD to test a series of pharmaceutical drugs chosen for their targeting of glutamate receptors. The use of these drugs may lead to a reduction in the neurodegenerative nature of VaD.

What are we trying to find out?

The clinical utility of a series of pharmaceutical drugs which act on glutamate receptors will be tested utilising a state-of-the-art in vitro model developed by this research group. The application of these drugs will be optimised for most effective treatment of dementia symptoms.

How will this be done?

The effect of a series of glutamate receptor drugs will be characterised using a series of laboratory techniques previously used by this research group.  These techniques will focus on analysing the amount of neurodegeneration that has occurring before and after the administering of selected pharmaceutical drugs. 

Why is this important?

Despite high prevalence, Vascular Dementia (VaD) is under researched in comparison to Alzheimer’s disease. This project has the potential to develop new treatments for VaD. A student will also gain expert technical knowledge in the study of these systems, attaining a range of skills suitable for a career in dementia research.

The vulnerability of white matter to induction of a human tau mutation associated with dementia (PhD Studentship)

Summary

This project seeks to understand the link between tau (a protein found in cells of dementia patients) and degradation of white matter in the brain. The propensity of white matter to undergo further damage due to malfunctioning ion channels will also be studied. This may provide a possible mechanism for the extensive degradation of neurones which cause the cognitive impairment characteristic of dementia.

What do we already know?

Abnormalities in the white matter (WM) of the brain is present in 60% of Alzheimer’s Disease (AD) and is one of the earliest indications of the disease. Production of a protein known as tau leads to changes in WM which may lead to dementia. These changes have been shown to involve the thinning of the myelin sheath, an insulating layer found on neurones, essential for normal function. Understanding the link between the production of tau and the consequent WM damage may have significant benefits for the treatment of dementia related diseases.

What are we trying to find out?

This project will focus on confirming the link between tau production and decline of the functionality of WM. Ischemic WM injury is associated with the malfunctioning of ion channels in neurones. Another aim of the project is to ascertain whether damaged WM has an increased propensity to undergo further ischemic neurone damage.

How will this be done?

The structure and function of WM after induction of tau will be monitored. The tolerance of WM cells to ischemic injury after tau induction will be measured. The ability of the WM to recover after tau protein production stops will also be tested.

Why is this important?

Abnormal tau protein is implicated in many different neurodegenerative diseases. This project seeks to understand how tau causes the neurodegenerative effects of dementia related diseases. This will provide an invaluable insight into the cause of the disease. This project also seeks to understand the risk of further injury to WM via ischemia (malfunctioning ion channels). This may be the process by which neurodegeneration continually gets worse leading to loss in cognitive function. Understanding the underlying causes of dementia is vitally important in developing a potential cure.

Glossary

Tau - Proteins that stabilise a cell component known as microtubules. In Alzheimer’s and Parkinson’s disease these tau proteins are defective and no longer functional.  
Clinical utility – The effectiveness of a drug to provoke its desired effect.
in vitro – From latin, defines a study which is conducted outside the living organism
Ischemic WM injury – A specific kind of injury to the white matter (WM) in the brain.
Myelin sheath – An essential part of the structure of the neurone, consisting of an insulating layer that surrounds the neurone.

Further Information 

Please click here for more information about the work of Professor Robert Fern.