Mechanistic impacts of bacterial diet on dopaminergic neurodegeneration in a Caenorhabditis elegans α-synuclein model of Parkinson's disease.

Autor:	Gaeta AL; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., Willicott K; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., Willicott CW; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., McKay LE; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., Keogh CM; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., Altman TJ; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., Kimble LC; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., Yarbrough AL; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA., Caldwell KA; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.; Center for Convergent Bioscience and Medicine, The University of Alabama, Tuscaloosa, AL 35487, USA.; Alabama Research Institute on Aging, The University of Alabama, Tuscaloosa, AL 35487, USA.; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Nathan Shock Center of Excellence for Basic Research in the Biology of Aging, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA., Caldwell GA; Department of Biological Sciences, The University of Alabama, Tuscaloosa, AL 35487, USA.; Center for Convergent Bioscience and Medicine, The University of Alabama, Tuscaloosa, AL 35487, USA.; Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, Nathan Shock Center of Excellence for Basic Research in the Biology of Aging, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 May 12; Vol. 26 (6), pp. 106859. Date of Electronic Publication: 2023 May 12 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.106859
Abstrakt:	Failure of inherently protective cellular processes and misfolded protein-associated stress contribute to the progressive loss of dopamine (DA) neurons characteristic of Parkinson's disease (PD). A disease-modifying role for the microbiome has recently emerged in PD, representing an impetus to employ the soil-dwelling nematode, Caenorhabditis elegans, as a preclinical model to correlate changes in gene expression with neurodegeneration in transgenic animals grown on distinct bacterial food sources. Even under tightly controlled conditions, hundreds of differentially expressed genes and a robust neuroprotective response were discerned between clonal C. elegans strains overexpressing human alpha-synuclein in the DA neurons fed either one of only two subspecies of Escherichia coli . Moreover, this neuroprotection persisted in a transgenerational manner. Genetic analysis revealed a requirement for the double-stranded RNA (dsRNA)-mediated gene silencing machinery in conferring neuroprotection. In delineating the contribution of individual genes, evidence emerged for endopeptidase activity and heme-associated pathway(s) as mechanistic components for modulating dopaminergic neuroprotection. Competing Interests: The authors declare no competing interests. (© 2023 The Author(s).)
Databáze:	MEDLINE
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