SPELL - S. cerevisiae

Citation	Chen X, Munoz-Arellano AJ, Petranovic D. UBB(+1) reduces amyloid-beta cytotoxicity by activation of autophagy in yeast. Aging, 2021.
PubMed ID	34751669
Short Description	UBB(+1) reduces amyloid-beta cytotoxicity by activation of autophagy in yeast.
# of Conditions	8
Full Description	UBB(+1) is a mutated version of ubiquitin B peptide caused by a transcriptional frameshift due to the RNA polymerase II "slippage". The accumulation of UBB(+1) has been linked to ubiquitin-proteasome system (UPS) dysfunction and neurodegeneration. Alzheimer's disease (AD) is defined as a progressive neurodegeneration and aggregation of amyloid-beta peptides (Abeta) is a prominent neuropathological feature of AD. In our previous study, we found that yeast cells expressing UBB(+1) at lower level display an increased resistance to cellular stresses under conditions of chronological aging. In order to examine the molecular mechanisms behind, here we performed genome-wide transcriptional analyses and molecular/cellular biology assays. We found that low UBB(+1) expression activated the autophagy pathway, increased vacuolar activity, and promoted transport of autophagic marker ATG8p into vacuole. Furthermore, we introduced low UBB(+1) expression to our humanized yeast AD models, that constitutively express Abeta42 and Abeta40 peptide, respectively. The co-expression of UBB(+1) with Abeta42 or Abeta40 peptide led to reduced intracellular Abeta levels, ameliorated viability, and increased chronological life span. In an autophagy deficient background strain (atg1Delta), intracellular Abeta levels were not affected by UBB(+1) expression. Our findings offer insights for reducing intracellular Abeta toxicity via autophagy-dependent cellular pathways under low level of UBB(+1) expression.
Tags	disease