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.

UBB+1

Alzheimer's disease

yeast

amyloid-beta

autophagy

Författare

Xin Chen

Chalmers, Biologi och bioteknik, Systembiologi

Ana Joyce Muñoz Arellano

Chalmers, Biologi och bioteknik, Systembiologi

Dina Petranovic Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Aging

19454589 (ISSN)

Vol. 13 21 23953-23980

Ämneskategorier

Biokemi och molekylärbiologi

Cell- och molekylärbiologi

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

DOI

10.18632/aging.203681

PubMed

34751669

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Senast uppdaterat

2023-03-21