UBB+1 reduces amyloid-beta cytotoxicity by activation of autophagy in yeast
Artikel i vetenskaplig tidskrift, 2021

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 (A beta) 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 A beta 42 and A beta 40 peptide, respectively. The co-expression of UBB+1 with A beta 42 or A beta 40 peptide led to reduced intracellular A beta levels, ameliorated viability, and increased chronological life span. In an autophagy deficient background strain (atg1 Delta), intracellular A beta levels were not affected by UBB+1 expression. Our findings offer insights for reducing intracellular A beta toxicity via autophagydependent cellular pathways under low level of UBB+1 expression.


Alzheimer's disease





Xin Chen

Chalmers, Biologi och bioteknik, Systembiologi

Ana Joyce Muñoz Arellano

Chalmers, Biologi och bioteknik, Systembiologi

Dina Petranovic Nielsen

Chalmers, Biologi och bioteknik, Systembiologi


1594-0667 (ISSN) 1720-8319 (eISSN)

Vol. 13 21 23953-23980


Biokemi och molekylärbiologi

Cell- och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)





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