Study Rationale: Parkinson’s Disease progresses with the death of nerve cells in the brain. Some forms of the disease run in families due to mutations in important genes. One of these genes is called alpha-synculein. This gene produces a protein that tends to form clumps which appear to spread in the brain as the disease advances. We study other genes, the SCAMPs, that may control that spread. By understanding how these genes work, we may find ways to help brain cells control α-syn clumps.
Hypothesis: The SCAMPs are found on membranes in nerve cells that deliver alpha-synculein to a part of the cell where proteins are broken down. Once we understand how the SCAMPs deliver alpha-synculein to this compartment, we will look for ways to make then work better on breaking down alpha-synculein clumps.
Study Design: We use human cells grown in the laboratory and fruitflies to study how alpha-synculein traffics in the brain. We found the SCAMPs in a search for targets on a cell membrane involved in the traffic of alpha-synculein. Dr. Feany’s lab has introduced the gene for human alpha-synculein into the fly brain and has found that this causes a walking defect in the fly. In collaboration, she has found that a defect in the fly SCAMP produces a profound walking defect and leads to more α-syn building up inside of the fly brain cells. We will now repeat this with human brain cells.
Impact on Diagnosis/Treatment of Parkinson’s disease: If the SCAMPs work the same way in human brain cells as in the fruitfly, we will look for treatments that speed the action of the SCAMPs in controlling alpha-synculein buildup. Such treatments could be the beginning of a search for drugs that have this effect in patients to help control the spread of alpha-synculein.
Next Steps for Development: One promising avenue is to explore the interaction of the SCAMPs with the exercise hormone irisin. Irisin has been reported to speed the removal of alpha-synculein clumps. If our investigation works, we will be able to help discover how irisin helps brain cells to destroy alpha-synculein clumps.