With substantial funding from Parkinson’s UK my research group created a model of neurodegeneration and Lewy-like inclusion formation in the brain that resembles Parkinson’s disease and dementia with Lewy bodies. This model is unique and is allowing us to investigate progressive changes in the brain that accompany disease, which we cannot do in humans. Models are an important contribution to human studies.
The ubiquitin proteasome system is the major pathway for the regulated degradation of most unwanted proteins in a cell. We found that if we inhibited this protein degradation in neurons this triggers neurodegeneration and Lewy-like inclusion formation. More recently, we have shown this also causes oxidative stress, another factor that is consistently linked to neurodegenerative disease. Our current research is focused on the role of mitochondria in neurodegeneration in this model. Again, mitochondria, the cells batteries, are one of the key hypotheses linked to neurodegenerative disease. We have already found that mitochondria are changed in our model and we want to understand whether these changes are particularly important in neurons. Models such as these are important to identify early changes in disease if we are to develop therapeutic intervention to help slow or stop its progression.