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Bacteria in the Digestive Tract May Trigger Protein Clumping, the Hallmark of Parkinsonís

In experiments with rats, scientists have shown that when nerve cells in the gut are exposed to certain bacteria, it may trigger protein-clumping similar to the clumping found in Parkinson’s disease (PD). The results suggest a possible way in which the protein clumping in PD might begin. The study appears in the October 6 online edition of Scientific Reports.

Alpha-synuclein is a protein found in nerve cells throughout the body. In PD, abnormal forms of this protein are found stuck together in toxic clumps called Lewy bodies. One theory states that Lewy bodies may first develop in the cells lining the digestive tract, before traveling from cell to cell (similar to an infection) and eventually reaching the brain. This mode of transmission is similar to infectious proteins called prions.

For the new study, researchers led by Robert P. Friedland, M.D., at the University of Louisville, asked, how could this process begin in the gut? They proposed that Lewy bodies might be “seeded” by a protein “template” generated by bacteria in the gut. To test the idea, they fed E. coli bacteria (Escherichia coli), which produce the protein clumping template called curli, to aged laboratory rats. Another group of rats was fed mutant E. coli that could not make the curli protein. In additional experiments, the researchers gave the E. coli to roundworms (a standard laboratory organism) engineered to produce human alpha-synuclein.

Results

  • The rats fed the curli-producing bacteria showed increased levels of alpha-synuclein in the intestines and the brain, and increased alpha-synuclein aggregation in the brain, compared with rats who were exposed to bacteria that did not produce the protein.
  • The rats exposed to curli had more inflammation in their brains — a sign associated with PD — than the control animals.
  • There were no differences between the rats in survival, body weight, or inflammation of the gut.
  • Roundworms that were fed curli-producing bacteria also showed an increase in alpha-synuclein clumps.

What Does It Mean?

The study suggests that abnormal protein production by gut bacteria and clumping in the gut may affect protein clumping in the rest of the body. Therefore, it is possible that such clumping might be one of the first events in the development of PD. Further research is needed to understand how and why this happens.  

The research joins a growing scientific literature exploring the role of bacteria and other organisms in the gut — the microbiome — in health and disease. It is among the few studies analyzing the influence of bacterial clumping proteins on disease in animals. A better understanding of these relationships could open avenues to new PD therapies.


Reference: Chen, S. G., Stribinskis, V., Rane, M. J., Demuth, D. R., Gozal, E., Roberts, A. M., et al. (2016). Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans. Scientific Reports, 6, 34477. http://doi.org/10.1038/srep34477

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Source Date: Nov 27 2016