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Interplay of Energe...
Interplay of Energetics and ER Stress Exacerbates Alzheimer's Amyloid-beta (A beta) Toxicity in Yeast
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- Chen, Xin, 1980 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Bisschops, Mark, 1985 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Agarwal, Nisha Rani, 1987 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Ji, Boyang, 1983 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Ponnandai Schanmugavel, Kumaravel, 1991 (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)
- 2017-07-27
- 2017
- English.
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In: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 10
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Abstract
Subject headings
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- Alzheimer's disease (AD) is a progressive neurodegeneration. Oligomers of amyloid-beta peptides (A beta) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of A beta associated with AD are A beta 40 and A beta 42, the latter being more toxic and prone to form oligomers. Here, we took a systems biology approach to study two humanized yeast AD models which expressed either A beta 40 or A beta 42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected chronological lifespan and reduced variations during cell growth. Reduced growth rates and biomass yields were observed upon A beta 42 expression, indicating a redirection of energy from growth to maintenance. Quantitative physiology analyses furthermore revealed reduced mitochondria' functionality and ATP generation in A beta 42 expressing cells, which matched with observed aberrant mitochondria' structures. Genome-wide expression level analysis showed that A beta 42 expression triggered strong ER stress and unfolded protein responses. Equivalent expression of A beta 40, however, induced only mild ER stress, which resulted in hardly affected physiology. Using AD yeast models in well controlled cultures strengthened our understanding on how cells translate different A beta toxicity signals into particular cell fate programs, and further enhance their potential as a discovery platform to identify possible therapies.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Keyword
- ER stress
- amyloid-beta
- Alzheimer's disease
- energetics
- yeast
Publication and Content Type
- art (subject category)
- ref (subject category)
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