Cytosolic amyloid-beta peptide 42 escaping from degradation induces cell death

Biochemical and Biophysical Research Communications
Eun Kyung LeeYung Joon Yoo

Abstract

Accumulating evidence suggests that intracellular amyloid-beta (Abeta) peptide triggers the early pathological events in Alzheimer's disease (AD). However, little is known about the consequence of cytosolic Abeta. In this study, we ectopically expressed Abeta42 in the cytoplasm of SH-SY5Y neuroblastoma cells by expressing a fusion protein of GFP-tagged ubiquitin and Abeta42 (GFPUb-Abeta42). Although GFPUb and Abeta42 are stochastically produced with the same molar ratio in the cytoplasm, Abeta42 was completely degraded in more than 50% of the GFPUb-expressing cells. However, if Abeta42 was not degraded in their cytoplasm, then Abeta42-expressing cells underwent apoptosis. The number of Abeta42-expressing cells is significantly increased by the inhibition of proteasome with MG132. Cytosolic Abeta42 which has escaped degradation inhibits proteasome and thereby may accelerate the accumulation of Abeta42 and its detrimental effects. Our findings suggest that cells have the potential to degrade Abeta42 in their cytoplasm but if Abeta42 appears in the cytoplasm due to its incomplete degradation, it accumulates and may trigger the fatal cascade of pathology of AD.

References

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Feb 28, 2002·The Journal of Biological Chemistry·Pascal Kienlen-CampardJean-Noël Octave
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Feb 22, 2005·Protein Expression and Purification·Eun Kyung LeeYung Joon Yoo
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Citations

Dec 6, 2012·Translational Neurodegeneration·Lin ZhengAlexei Terman
Aug 21, 2013·Alzheimer's Research & Therapy·Malcolm A Leissring, Anthony J Turner
Dec 11, 2007·Neurobiology of Aging·Doris CulpanSeth Love
Mar 2, 2018·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Saak V OvsepianJ Oliver Dolly
May 1, 2021·International Journal of Molecular Sciences·Alexander G BobylevIvan M Vikhlyantsev
Aug 20, 2021·Aging Cell·Eduardo J Fernandez-PerezLuis G Aguayo

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