1. Mechanistic impacts of bacterial diet on dopaminergic neurodegeneration in a Caenorhabditis elegans α-synuclein model of Parkinson’s disease
- Author
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Anthony L. Gaeta, Karolina Willicott, Corey W. Willicott, Luke E. McKay, Candice M. Keogh, Tyler J. Altman, Logan C. Kimble, Abigail L. Yarbrough, Kim A. Caldwell, and Guy A. Caldwell
- Subjects
Neuroscience ,Cognitive neuroscience ,Science - 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.
- Published
- 2023
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