title: Cytosolic amyloid-beta peptide 42 escaping from degradation induces cell death.
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.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Yong Wook
authors.initials: YW
authors.lastname: Park
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Shin
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
authors.forename: Yung Joon
authors.initials: YJ
authors.lastname: Yoo
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D017209:Apoptosis; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D010446:Peptide Fragments / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)