Alzheimer's disease-associated amyloid beta interacts with the human serine protease HtrA2/Omi.
Amyloid beta (Abeta), a principle component of the cerebral plaques found in the brains of patients with Alzheimer's disease (AD), is a pivotal factor implicated in the pathogenesis of AD. Recent reports show that not only extracellular Abeta but also intracellular Abeta induces neuronal apoptosis; however, the mechanism remains to be elucidated. Using yeast two-hybrid assays, we found that Abeta interacts with HtrA2/Omi, an essential human serine protease with proapoptotic activity. Additionally, we mapped the C-terminal region containing the PDZ domain of HtrA2/Omi as the binding determinant for Abeta? The interaction of Abeta with HtrA2/Omi was further confirmed through in vivo co-immunoprecipitation assay in HEK293 cells. This study suggests the possibility that the accumulation of intracellular Abeta and a function of proapoptotic protease, HtrA2/Omi are correlated.
Park
Hyo-Jin
HJ
Graduate School of Biotechnology, Korea University, Seoul 136-701, South Korea.
Seong
Young-Mo
YM
Choi
Ju-Youn
JY
Kang
Seongman
S
Rhim
Hyangshuk
H
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001665:Binding Sites / Q000502:physiology; D002460:Cell Line; D000074923:High-Temperature Requirement A Serine Peptidase 2; D006801:Humans; D024101:Mitochondrial Proteins; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D024101:Mitochondrial Proteins; D012697:Serine Endopeptidases; C000615914:HTRA2 protein, human; D000074923:High-Temperature Requirement A Serine Peptidase 2