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Mechanistic impacts of bacterial diet on dopaminergic neurodegeneration in a Caenorhabditis elegans α-synuclein model of Parkinson’s disease
- Source :
- iScience, Vol 26, Iss 6, Pp 106859- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Summary: 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.
- Subjects :
- Neuroscience
Cognitive neuroscience
Science
Subjects
Details
- Language :
- English
- ISSN :
- 25890042
- Volume :
- 26
- Issue :
- 6
- Database :
- Directory of Open Access Journals
- Journal :
- iScience
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.110ccf8d94304ef59fa69e95a0718c71
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.isci.2023.106859