Motor Proteins as Novel Drug Targets of Disease-modifying Treatments for Parkinson’s Disease

Objective/Rationale:
More and more research suggests that part of the cellular quality control mechanism, which degrades abnormal proteins or damaged parts of the cell, is defective in Parkinson’s disease (PD). The proteins parkin and PINK1, which are often mutated in familial PD, play a central role in eliminating damaged mitochondria, the powerhouses of the cell. In this project, we are identifying and investigating novel regulators in this crucial quality control pathway.

Project Description:
Research in our lab is focused on motor proteins, which are molecular machines that drive cargo along tracks to specific sites in the cell, like a train running along a railway network to its specific destinations. New results now show that these molecular motor proteins may play a crucial role in the pathway that eliminates damaged mitochondria. In this project, we will use a number of techniques to identify how these motor proteins or its cargo hooks associate with the machinery that mediates cellular quality control. In addition, we will test whether eliminating the molecular motors inhibits turnover of damaged cell parts leading to an accumulation of non-functional mitochondria and reduced energy production. 

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Motor proteins are attractive targets for small molecule inhibitors and also activators. Thus, motor proteins are a rare example where specific drugs have been developed that can either inhibit or activate enzymatic motor activity. In this project, we will test the effect of the available inhibitors for motor proteins on clearance of mitochondria and validate specific motor proteins as potential drug targets to develop novel therapies for PD. 

Anticipated Outcome:
The outcomes from this research will establish whether molecular motors and their cargo adaptors play essential roles in the pathway important for clearing damaged mitochondria, especially from brain cells. This will open up new areas of research that may guide future clinical studies and the development of potential diagnostic tools and possible therapeutic strategies.