Affiliation:
1. Croatian Institute for Brain Research, University of Zagreb School of Medicine Zagreb Croatia
2. Nash Family Department of Neuroscience, Ronald M. Loeb Center for Alzheimer's Disease Friedman Brain Institute, Icahn School of Medicine at Mount Sinai New York New York USA
Abstract
AbstractBackgroundThe primary histological characteristic of Alzheimer's disease is the presence of neurofibrillary tangles, which are large aggregates of tau protein. Aging is the primary risk factor for the development of Alzheimer's disease, however, the underlying causes of tau protein aggregation and toxicity are unclear.AimsHere we investigated tau aggregation and toxicity under the conditions of compromised protein homeostasis.MethodsWe used heterologous expression of human tau protein in the unicellular eukaryote yeast Saccharomyces cerevisiae with evolutionarily conserved protein quality control pathways and examined tau‐dependent toxicity and aggregation using growth assays, fluorescence microscopy, and a split luciferase‐based reporter NanoBiT.ResultsTau protein expressed in yeast under mild proteotoxic stress, or in mutants with impaired pathways for proteotoxic stress response, did not lead to synthetic toxicity or the formation of obvious aggregates. Chronologically old cells also did not develop observable tau aggregates. Our examination of tau oligomerization in living cells using NanoBiT reporter suggests that tau does not form significant levels of oligomers under basal conditions or under mild proteotoxic stress.ConclusionTogether our data suggest that human tau protein does not represent a major burden to the protein quality control system in yeast cells.
Funder
Hrvatska Zaklada za Znanost
European Commission
European Social Fund
European Regional Development Fund
Subject
Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献