Our sponsored Ph.D. student describes her project:
“My PhD project investigates genes and molecular processes which might lead to dementia with Lewy bodies (DLB) and Parkinson’s disease (PD), focusing on the glucocerebrosidase (GBA) gene. It has recently been suggested that the presence of a faulty GBA gene contributes to the risk of developing DLB and PD, however the mechanism for that association is unknown.
During my studies I have found that DLB and PD patients from North East England are not more likely to have aGBA gene mutation than neurologically healthy individuals. This might indicate that the GBA gene is only a major risk factor in certain populations. Whilst we did not find increased risk with the GBA gene, it is possible that those individuals who do carry mutations in the gene have a predisposition to DLB. In order to study the mechanism of potential contribution of GBA to DLB, I analysed brain tissues from the GBA mutation carriers and compared them to non-carriers. Interestingly, the investigation has revealed abnormalities in the brain in patients and controls that had the faulty GBA gene which might cause them to produce abnormally folded proteins which are known to build up in the brains of people with DLB. Further investigation of this may help us to understand the pathologic mechanism for GBA contribution to DLB and tell us what may help to protect against Lewy body dementia. ”
Update from Marzena 18 January 2011 :
During my PhD studies I have found the presence of mutations in the glucocerebrosidase (GBA) gene in a small proportion of patients with dementia with Lewy bodies and also in neurologically healthy individuals. These mutations may lead to changes in cellular functions predisposing to nerve cell damage and development of Lewy Body Disease. Currently, I am working on a stem cell model of the GBA pathology which aims to reproduce my previous findings in brain tissue.
I am also investigating whether the brain is more sensitive to the effects of GBA mutations than other organs. My preliminary results imply that there may be a reduction of protective sugar residues that are present in normal GBA protein but only when it is found in the brain which makes the brain GBA enzyme more vulnerable to damage. This interesting finding needs further evaluation and it might have potential implications for possible therapeutic options which are currently being used to treat severe GBA deficiency.