University of Bristol - Dr Daniel Whitcomb
Are neuronal catenins involved in the synaptopathology of Alzheimer’s disease? (Pilot Grant)
See glossary at bottom of page for definition of underlined words.
The loss of connection between neurones in the brain is believed to be one of the causes of Alzheimer’s disease. The role of a specific protein (catenin) in the breakdown of the connectivity between neurones is not known. This project seeks to utilise a series of molecular biology techniques to test the role of catenins in those suffering with dementia related diseases. In the future, catenins present themselves as a promising therapeutic target for dementia treatment.
What do we already know?
Dementia is believed to be caused by loss of connections between neurones in the brain. A specific class of molecules known as cell adhesion molecules (CAM’s) have been found to be vital in maintaining neuronal connections in the brain. CAM’s themselves have been found to be regulated by a family of proteins known as catenins. Amyloid-β (Aβ) is a key protein in Alzheimer’s disease (AD) and has been shown to break down catenins leading to a loss of neurone connectivity (summarised in Figure 1).
What are we trying to find out?
This project will look to find out whether catenin proteins are deficient in the brains of people who suffer from AD compared to those who do not. The effect of Aβ on catenins will also be investigated and the link between CAM’s and catenins will also be studied in further detail.
How will this be done?
Several molecular biology techniques will be used to identify the proteins found in brains of AD sufferers. Further techniques will allow the quantity of each protein to be measured. Comparison of catenin levels between AD sufferers and control groups will allow the links between catenin levels and onset of AD to be determined.
Why is this important?
This study will increase the understanding about the roles of different proteins within AD brains. The understanding of dementia on a general level will be increased and this could lead the way in highlighting catenins as important targets for potential dementia treating drugs.
Catenins – A class of proteins responsible for the production of cell adhesion molecues (CAM’s) among other things.
Cell adhesion molecules (CAM) - A class of small proteins which are essential for the normal functioning of neurones.
Amyloid-β - A peptide (small protein) which has been found to build up in brain cells of sufferers of Alzheimer’s disease. Amyloid-β will aggregate and form amyloid plaques which have been found to interfere with normal function of cells and tissues.
Control Group – A group of test subjects which are left unexposed to compare with treated subjects. In this scenario the control group indicates a group of individuals who do not suffer from Alzheimer’s disease.
Figure 1: A figure showing how the interaction between cadherin (the cell adhesion molecule) and catenin maintains the link between neurons in the brain.
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