title: Role of frameshift ubiquitin B protein in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common neurodegenerative disease and is characterized by accumulation of misfolded and aggregated proteins. Since the ubiquitin-proteasome system (UPS) is the major intracellular protein quality control (PQC) system in eukaryotic cells, it is likely involved in the etiology of AD. The frameshift form of ubiquitin (Ubb(+1) ) accumulates in the neuritic plaques and neurofibrillary tangles in patients with AD. Ubb(+1) accumulates in an age-dependent manner as a result of RNA-polymerase mediated molecular misreading during transcription, which allows the formation of mutant proteins in the absence of gene mutations. The accumulation of the Ubb(+1) protein may act as an endogenous reporter for proteasome dysfunction and a growing number of studies have shown that Ubb(+1) may play more important pathogenic roles in AD etiology than previously hypothesized. The yeast Saccharomyces cerevisiae shares many conserved biological processes with all eukaryotic cells, including human neurons. This organism has been regarded as a model system for investigating the fundamental intracellular mechanisms, including those underlying neurodegeneration. We propose here that yeast systems biology approaches, combined with cell and molecular biology approaches will increase the relevant knowledge needed for advancement and elucidation of mechanisms and complex traits, which could provide new targets for therapeutic intervention in AD. WIREs Syst Biol Med 2016, 8:300-313. doi: 10.1002/wsbm.1340 For further resources related to this article, please visit the WIREs website.
authors.affiliation: Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Systems and Synthetic Biology, Department of Biology and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden.|Novo Nordisk Foundation Center for Biosustainability, Chalmers University of Technology, Göteborg, Sweden.
authors.forename: Dina
authors.initials: D
authors.lastname: Petranovic
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D016368:Frameshift Mutation; D006801:Humans; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000235:genetics* / Q000378:metabolism
chemical_list: C479419:UBB protein, human; D025801:Ubiquitin; D012321:DNA-Directed RNA Polymerases; D046988:Proteasome Endopeptidase Complex