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

Diseases
Medicine

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