title: Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans.
abstract: Misfolded alpha-synuclein (AS) and other neurodegenerative disorder proteins display prion-like transmission of protein aggregation. Factors responsible for the initiation of AS aggregation are unknown. To evaluate the role of amyloid proteins made by the microbiota we exposed aged rats and transgenic C. elegans to E. coli producing the extracellular bacterial amyloid protein curli. Rats exposed to curli-producing bacteria displayed increased neuronal AS deposition in both gut and brain and enhanced microgliosis and astrogliosis compared to rats exposed to either mutant bacteria unable to synthesize curli, or to vehicle alone. Animals exposed to curli producing bacteria also had more expression of TLR2, IL-6 and TNF in the brain than the other two groups. There were no differences among the rat groups in survival, body weight, inflammation in the mouth, retina, kidneys or gut epithelia, and circulating cytokine levels. AS-expressing C. elegans fed on curli-producing bacteria also had enhanced AS aggregation. These results suggest that bacterial amyloid functions as a trigger to initiate AS aggregation through cross-seeding and also primes responses of the innate immune system.
authors.affiliation: Dept. of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Shu G
authors.initials: SG
authors.lastname: Chen
authors.affiliation: Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Vilius
authors.initials: V
authors.lastname: Stribinskis
authors.affiliation: Dept. of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Madhavi J
authors.initials: MJ
authors.lastname: Rane
authors.affiliation: Dept. of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, Kentucky, USA.
authors.forename: Donald R
authors.initials: DR
authors.lastname: Demuth
authors.affiliation: Dept. of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Gozal
authors.affiliation: Dept. of Physiology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Roberts
authors.affiliation: Dept. of Pediatrics, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Rekha
authors.initials: R
authors.lastname: Jagadapillai
authors.affiliation: Dept. of Neurology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Ruolan
authors.initials: R
authors.lastname: Liu
authors.affiliation: Dept. of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Kyonghwan
authors.initials: K
authors.lastname: Choe
authors.affiliation: Dept. of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Bhooma
authors.initials: B
authors.lastname: Shivakumar
authors.affiliation: Dept. of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Francheska
authors.initials: F
authors.lastname: Son
authors.affiliation: Dept. of Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Shunying
authors.initials: S
authors.lastname: Jin
authors.affiliation: Dept. of Epidemiology and Population Health, University of Louisville School of Public Health, Louisville, Kentucky, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Kerber
authors.affiliation: Laboratory of Experimental Neuropathology, University of California, San Diego, California, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Adame
authors.affiliation: Laboratory of Experimental Neuropathology, University of California, San Diego, California, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.affiliation: Dept. of Neurology, University of Louisville School of Medicine, Louisville, Kentucky, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Friedland
mesh_terms: D000682:Amyloid / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000378:metabolism*; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000494:pharmacology*; D066263:Protein Aggregation, Pathological / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D000682:Amyloid; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C497606:Snca protein, rat; D051844:alpha-Synuclein; C077481:Crl protein, Bacteria