Generation and characterization of a tractable C. elegans model of tauopathy.
Alzheimer's disease
C. elegans
Genetic screening tool
Healthspan
Lifespan
Tauopathy
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
06
04
2021
accepted:
09
08
2021
pubmed:
19
9
2021
medline:
27
1
2022
entrez:
18
9
2021
Statut:
ppublish
Résumé
Alzheimer's disease(AD) is an age-associated neurodegenerative disease that results in deterioration of memory and cognitive function. As a currently untreatable disorder, AD has emerged as one of the defining biomedical challenges of our time. Thus, new approaches that can examine the cellular and molecular mechanisms underlying age-related AD pathology are sorely needed. One of the hallmarks of Alzheimer's disease is the hyperphosphorylation of the tau protein. Caenorhabditis elegans have been previously used to study the genetic pathways impacted by tau proteotoxic stress; however, currently, available C. elegans tau models express the human protein solely in neurons, which are unresponsive to global RNA interference (RNAi). This limits powerful RNAi screening methods from being utilized effectively in these disease models. Our goal was to develop a C. elegans tau model that has pronounced tau-induced disease phenotypes in cells that can be modified by feeding RNAi methods. Towards this end, we generated a novel C. elegans transgenic line with codon-optimized human 0N4R V337M tau expressed in the body wall muscle under the myo-3 promoter. Immunoblotting experiments revealed that the expressed tau is phosphorylated on epitopes canonically associated with human AD pathology. The tau line has significantly reduced health metrics, including egg laying, growth rate, paralysis, thrashing frequency, crawling speed, and lifespan. These defects are suppressed by RNAi directed against the tau mRNA. Taken together, our results suggest that this alternative tau genetic model could be a useful tool for uncovering the mechanisms that influence the hyperphosphorylation and toxicity of human tau via RNAi screening and other approaches.
Identifiants
pubmed: 34536202
doi: 10.1007/s11357-021-00436-9
pii: 10.1007/s11357-021-00436-9
pmc: PMC8599767
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2621-2631Subventions
Organisme : NIA NIH HHS
ID : F32 AG054098
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013280
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG061132
Pays : United States
Informations de copyright
© 2021. American Aging Association.
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