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   Study demonstrates role of gut bacteria in neurodegenerative diseases   
      
   Date:   
   October 6, 2016   
   Source:   
   University of Louisville   
   Summary:   
   Exposure to bacterial proteins called amyloid that have structural similarity   
   to brain proteins may lead to an increase in clumping of proteins in the   
   brain, research has revealed. Aggregates of misfolded amyloid proteins are   
   seen in the brains of    
   patients with neurodegenerative diseases.   
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   FULL STORY   
   Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral   
   Sclerosis (ALS) are all characterized by clumped, misfolded proteins and   
   inflammation in the brain. In more than 90 percent of cases, physicians and   
   scientists do not know what    
   causes these processes to occur.   
      
      
   Robert P. Friedland, M.D., the Mason C. and Mary D. Rudd Endowed Chair and   
   Professor of Neurology at the University of Louisville School of Medicine, and   
   a team of researchers have discovered that these processes may be triggered by   
   proteins made by our    
   gut bacteria (the microbiota). Their research has revealed that exposure to   
   bacterial proteins called amyloid that have structural similarity to brain   
   proteins leads to an increase in clumping of the protein alpha-synuclein in   
   the brain. Aggregates, or    
   clumps, of misfolded alpha-synuclein and related amyloid proteins are seen in   
   the brains of patients with the neurodegenerative diseases AD, PD and ALS.   
      
   Alpha-synuclein (AS) is a protein normally produced by neurons in the brain.   
   In both PD and AD, alpha-synuclein is aggregated in a clumped form called   
   amyloid, causing damage to neurons. Friedland has hypothesized that similarly   
   clumped proteins produced    
   by bacteria in the gut cause brain proteins to misfold via a mechanism called   
   cross-seeding, leading to the deposition of aggregated brain proteins. He also   
   proposed that amyloid proteins produced by the microbiota cause priming of   
   immune cells in the    
   gut, resulting in enhanced inflammation in the brain.   
      
   The research, which was supported by The Michael J. Fox Foundation, involved   
   the administration of bacterial strains of E. coli that produce the bacterial   
   amyloid protein curli to rats. Control animals were given identical bacteria   
   that lacked the    
   ability to make the bacterial amyloid protein. The rats fed the    
   urli-producing organisms showed increased levels of AS in the intestines and   
   the brain and increased cerebral AS aggregation, compared with rats who were   
   exposed to E. coli that did not    
   produce the bacterial amyloid protein. The curli-exposed rats also showed   
   enhanced cerebral inflammation.   
      
   Similar findings were noted in a related experiment in which nematodes   
   (Caenorhabditis elegans) that were fed curli-producing E. coli also showed   
   increased levels of AS aggregates, compared with nematodes not exposed to the   
   bacterial amyloid. A research    
   group led by neuroscientist Shu G. Chen, Ph.D., of Case Western Reserve   
   University, performed this collaborative study.   
      
   This new understanding of the potential role of gut bacteria in    
   eurodegeneration could bring researchers closer to uncovering the factors   
   responsible for initiating these diseases and ultimately developing preventive   
   and therapeutic measures.   
      
   "These new studies in two different animals show that proteins made by   
   bacteria harbored in the gut may be an initiating factor in the disease   
   process of Alzheimer's disease, Parkinson's disease and ALS," Friedland said.   
   "This is important because most    
   cases of these diseases are not caused by genes, and the gut is our most   
   important environmental exposure. In addition, we have many potential   
   therapeutic options to influence the bacterial populations in the nose, mouth   
   and gut."   
      
   Friedland is the corresponding author of the article, "Exposure to the   
   functional bacterial amyloid protein curli enhances alpha-synuclein   
   aggregation in aged Fischer 344 rats and Caenorhabditis elegans," published   
   online Oct. 6 in Scientific Reports, a    
   journal of the Nature Publishing Group. UofL researchers involved in the   
   publication in addition to Friedland include Vilius Stribinskis, Ph.D.,   
   Madhavi J. Rane, Ph.D., Donald Demuth, Ph.D., Evelyne Gozal, Ph.D., Andrew M.   
   Roberts, Ph.D., Rekha    
   Jagadapillai, Ruolan Liu, M.D., Ph.D., and Richard Kerber, Ph.D. Additional   
   contributors on the publication include Eliezer Masliah, M.D., Ph.D. of the   
   University of California San Diego.   
      
   This work supports recent studies indicating that the microbiota may have a   
   role in disease processes in age-related brain degenerations. It is part of   
   Friedland's ongoing research on the relationship between the microbiota and   
   age-related brain    
   disorders, which involves collaborations with researchers in Ireland and Japan.   
      
   "We are pursuing studies in humans and animals to further evaluate the   
   mechanisms of the effects we have observed and are exploring the potential for   
   the development of preventive and therapeutic strategies," Friedland said.   
      
      
   Story Source:   
      
   Materials provided by University of Louisville. Note: Content may be edited   
   for style and length.   
      
   Journal Reference:   
      
   Shu G. Chen, Vilius Stribinskis, Madhavi J. Rane, Donald R. Demuth, Evelyne   
   Gozal, Andrew M. Roberts, Rekha Jagadapillai, Ruolan Liu, Kyonghwan Choe,   
   Bhooma Shivakumar, Francheska Son, Shunying Jin, Richard Kerber, Anthony   
   Adame, Eliezer Masliah, Robert    
   P. Friedland. Exposure to the Functional Bacterial Amyloid Protein Curli   
   Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and   
   Caenorhabditis elegans. Scientific Reports, 2016; 6: 34477 DOI:    
   0.1038/srep34477   
   Cite This Page:   
   MLA   
   APA   
   Chicago   
   University of Louisville. "Study demonstrates role of gut bacteria in   
   neurodegenerative diseases." ScienceDaily. ScienceDaily, 6 October 2016.   
   .   
      
      
       
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