Morphologic and Functional Effects of Gamma Secretase Inhibition on Splenic Marginal Zone B Cells
Joint Authors
Altmann, Bernd
Flohr, Alexander
de Vera Mudry, Maria Cristina
Müller, Lutz
Ozmen, Laurence
Festag, Matthias
Singer, Thomas
Jacobsen, Helmut
Regenass-Lechner, Franziska
Source
International Journal of Alzheimer's Disease
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-12-17
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
The γ-secretase complex is a promising target in Alzheimer’s disease because of its role in the amyloidogenic processing of β-amyloid precursor protein.
This enzyme also catalyzes the cleavage of Notch receptor, resulting in the nuclear translocation of intracellular Notch where it modulates gene transcription.
Notch signaling is essential in cell fate decisions during embryogenesis, neuronal differentiation, hematopoiesis, and development of T and B cells, including splenic marginal zone (MZ) B cells.
This B cell compartment participates in the early phases of the immune response to blood-borne bacteria and viruses.
Chronic treatment with the oral γ-secretase inhibitor RO4929097 resulted in dose-dependent decreased cellularity (atrophy) of the MZ of rats and mice.
Significant decreases in relative MZ B-cell numbers of RO4929097-treated animals were confirmed by flow cytometry.
Numbers of MZ B cells reverted to normal after a sufficient RO4929097-free recovery period.
Functional characterization of the immune response in relation to RO4929097-related MZ B cell decrease was assessed in mice vaccinated with inactivated vesicular stomatitis virus (VSV).
Compared with the immunosuppressant cyclosporin A, RO4929097 caused only mild and reversible delayed early neutralizing IgM and IgG responses to VSV.
Thus, the functional consequence of MZ B cell decrease on host defense is comparatively mild.
American Psychological Association (APA)
de Vera Mudry, Maria Cristina& Regenass-Lechner, Franziska& Ozmen, Laurence& Altmann, Bernd& Festag, Matthias& Singer, Thomas…[et al.]. 2012. Morphologic and Functional Effects of Gamma Secretase Inhibition on Splenic Marginal Zone B Cells. International Journal of Alzheimer's Disease،Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-460660
Modern Language Association (MLA)
de Vera Mudry, Maria Cristina…[et al.]. Morphologic and Functional Effects of Gamma Secretase Inhibition on Splenic Marginal Zone B Cells. International Journal of Alzheimer's Disease No. 2012 (2012), pp.1-7.
https://search.emarefa.net/detail/BIM-460660
American Medical Association (AMA)
de Vera Mudry, Maria Cristina& Regenass-Lechner, Franziska& Ozmen, Laurence& Altmann, Bernd& Festag, Matthias& Singer, Thomas…[et al.]. Morphologic and Functional Effects of Gamma Secretase Inhibition on Splenic Marginal Zone B Cells. International Journal of Alzheimer's Disease. 2012. Vol. 2012, no. 2012, pp.1-7.
https://search.emarefa.net/detail/BIM-460660
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-460660