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UBB+1 reduces amylo...
UBB+1 reduces amyloid-beta cytotoxicity by activation of autophagy in yeast
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- Chen, Xin, 1980 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Muñoz Arellano, Ana Joyce, 1983 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Petranovic Nielsen, Dina, 1975 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- 2021-11-09
- 2021
- English.
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In: Aging. - : Impact Journals, LLC. - 1945-4589. ; 13:21, s. 23953-23980
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- UBB+1
- Alzheimer's disease
- yeast
- amyloid-beta
- autophagy
Publication and Content Type
- art (subject category)
- ref (subject category)
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