test
Search publications, data, projects and authors
Characterisation of Transgenic C. elegans Alzheimer models, expressing the Human Tau protein in their GABAergic motonones

Thesis

French

ID: <10670/1.c8pdxn>

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by two hallmarks: extracellular plaques composed of amyloid-β (Aβ) deposits and intraneuronal accumulation of hyper and abnormal phosphorylated tau, also called neurofibrillary tangles (NFT). Despite many decades of research, the nature hypophosphorylated or hyperphosphorylated Tau toxicity remains ill understood. Our research project aims to characterize which state of Tau phosphorylation contributes to neuronal toxicity and identify the underlying mechanisms. To assess these objectives, we generated transgenic C. elegans models expressing either a human hyperphosphorylated tau (incorporation of 12 glutamate residues to mimic Tau hyperphosphorylation found in AD’s patients) human wild type Tau, or a human hypophosphorylated tau (incorporation of 12 alanine residues to mimic Tau hypophosphorylation) in the GABAergic motoneurons. Then, to characterize our models, we measured their behavior mainly with locomotion’s test using WormLab software. Our results showed that hyperphosphorylation of tau is the most toxic species for our models because hyperP strain showed an impair in the locomotor system translating into neurodegeneration, as well as developmental problems such as worm length. Then we tested some drugs used in taupathies C. elegans models to see if we could identify some biological pathways implicated in the toxicity. To conclude, our models may be a useful tool to identify genetic and pharmacological modifiers of tau toxicity.

Your Feedback

Please give us your feedback and help us make GoTriple better.
Fill in our satisfaction questionnaire and tell us what you like about GoTriple!