| RRC ID |
80856
|
| Author |
Gaeta AL, Willicott K, Willicott CW, McKay LE, Keogh CM, Altman TJ, Kimble LC, Yarbrough AL, Caldwell KA, Caldwell GA.
|
| Title |
Mechanistic impacts of bacterial diet on dopaminergic neurodegeneration in a Caenorhabditis elegans α-synuclein model of Parkinson's disease.
|
| Journal |
iScience
|
| Abstract |
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.
|
| Volume |
26(6)
|
| Pages |
106859
|
| Published |
2023-6-16
|
| DOI |
10.1016/j.isci.2023.106859
|
| PII |
S2589-0042(23)00936-7
|
| PMID |
37260751
|
| PMC |
PMC10227375
|
| Resource |
| C.elegans |
tm6801
tm1200 |
