Study Rationale: Parkinson’s disease (PD) 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 produces a protein called alpha-synuclein, which tends to form clumps that spread within the brain as the disease advances. We are currently studying SCAMPs, proteins that are found on membranes that deliver alpha-synuclein to a part of the cell where proteins are broken down. Their presence in neurons appears to minimize alpha-synuclein spread. By understanding how SCAMPs work, we may find ways to help brain cells control alpha-synuclein aggregation.
Hypothesis: We hypothesize that understanding how SCAMPs deliver proteins to a compartment where they can be degraded, we can find ways to make then work better on breaking down alpha-synuclein clumps.
Study Design: We will study how alpha-synuclein is trafficked in the brain using human cells grown in the laboratory and fruit flies. We discovered SCAMPs in a search for proteins involved in the traffic of alpha-synuclein. Dr. Feany’s lab introduced the gene for human alpha-synuclein into the fly brain and found that this manipulation disrupts the fly’s ability to walk. In a collaboration, she has found that a defect in the fruit fly version of SCAMP produces a profound walking defect and leads to increased alpha-synuclein buildup in fly brain cells. We will now repeat this experiment with human brain cells.
Impact on Diagnosis/Treatment of Parkinson’s disease: If SCAMPs function in human brain cells as they do in the fruit fly, we will look for treatments that enhance the ability of SCAMPs to control alpha-synuclein buildup. Such treatments could facilitate the search for drugs that have the same effect in people with PD.
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-synuclein clumps. If our study succeeds, we will be able to help discover how irisin helps brain cells to destroy alpha-synuclein clumps.