Name of Institution:
Harvard Medical School & Brigham and Women’s Hospital
Project Title:
Differential detection of physiological and pathological alpha synuclein
Investigator:
Tim Bartels, PhD
Dr. Bartels’ lab is dedicated to the research of protein folding in health and disease; specifically the investigation of the mis-folding pathways of alpha synuclein. As a PhD student at the Laboratory for Neurodegenerative Disease Research in Munich, Dr. Bartels work focused principally on biophysical techniques for investigating lipid structures and their interaction with alpha synuclein. Working with Dennis Selkoe at Harvard Medical School and Brigham and Women’s Hospital, Dr. Bartels observed scientists and clinicians with different backgrounds on the cell biology of alpha synuclein which further ignited his interest in both conceptual and experimental aspects of biochemical science and ultimately encouraged him to extend his focus on Parkinson’s Disease using a completely different set of techniques. Dr. Bartels has since been appointed Assistant Professor in Neurology at Harvard Medical School.
Research Objectives and Relevance to Diagnosis/Treatment of PD:
Understanding the exact mechanism of alpha synuclein dysfunction will lead to a better understanding of the molecular pathways in Parkinson’s Disease and will allow targeted drug design to correct these. In addition, the detection of pathological “prion-like” species could be used as a biomarker to aid early diagnosis. This study will try to characterize pathology associated forms of alpha synuclein to understand more about the mechanism of Parkinson’s Disease pathogenesis and quantify their abundance as a potential biomarker.
2016 Progress Update:
Good progress in testing patient samples for abnormal protein forms that are associated with causing Parkinson’s Disease has been made. The team found in a cohort of 12 Parkinson’s Disease and 12 healthy control subjects that only the disease associated samples contained soluble abnormal alpha synuclein forms and started characterizing these by structure and toxicity.
In a second project, the team analyzed factors that make the normal protein forms susceptible to abnormal changes in the case of PD. Thereby determining the very first events that happen in the pathogenesis of PD. The analysis showed that factors associated with increased risk of Parkinson’s Disease facilitate to a defined structural change in the protein. The team is currently looking into small molecules that would counteract this structural change and thereby are potential therapeutics for PD.