This grant builds upon the research from a prior grant: The Influence of Bacterial Amyloid on Alpha-synuclein Misfolding in a Pre-clinical Model
Promising Outcomes of Original Grant:
We hypothesized that that deposits of the Parkinson’s disease-associated protein alpha-synuclein in gut and brain neurons are caused by exposure to proteins of similar structure that are contained in bacteria that reside in the mouth and gut. Our results show that aged pre-clinical models given bacteria making an amyloid protein have more inflammation in the brain and also more alpha-synuclein deposits in the brain and gut than animals receiving control bacteria.
Objectives for Supplemental Investigation:
We will carry out further studies on the material obtained from the investigations supported by the original project. The distribution in space in the brain and gut will be analyzed and the chemical nature of the protein changes will be assessed. We will specifically asses the three-dimensional structure of the protein deposits observed. We will also measure the presence of changes in markers of inflammation and free radicals in brain and gut. Changes in other tissues — including the eyes, kidneys and hearts — will also be investigated. We will also complete electron microscopic studies of protein deposits in gut neurons.
Importance of This Research for the Development of a New PD Therapy:
At the moment there is no way to prevent or lower the risk of developing PD. It may be possible to alter disease risk and/or treat the disease by altering exposure in the intestine to amyloid-containing bacteria. This might be done through diet, prebiotics (which alter the growth of bacteria in the intestine by providing food for the bacteria) or probiotics (which directly supply desired bacteria to the intestine). Our study will point to the importance of the bacteria residing in our intestines for human health and disease. The results will be valuable for development of preventive and therapeutic strategies.