Ubiquitin Conjugates in Parkinson's Disease and Dementia with Lewy Bodies

To adapt to the ever-changing environment, the cell has to consistently make new proteins and degrade those that are no longer needed or toxic to the cell. Removal of intracellular proteins is primarily carried out by the ubiquitin-proteasome system, where proteins are tagged with a small protein called ubiquitin to form ubiquitin conjugates. Normally, ubiquitin conjugates are rapidly degraded so that abnormal or toxic proteins are kept at the minimum in cells. In Parkinson's disease however, ubiquitin conjugates accumulate in neurons to form large protein clumps called Lewy bodies. This project aims to use a proteomic approach to systemically document ubiquitin-conjugated proteins, which accumulate in brains in Parkinson's disease and the related disease dementia with Lewy bodies. The nature and molecular pathology of ubiquitin-conjugates will be characterized to determine why they are not as efficiently degraded by neurons. The information from this study may be useful for the design of strategies to enhance the removal of abnormal proteins from neurons affected by Parkinson's disease.