Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke

Thiruma V. Arumugam; Sic L. Chan; Dong Gyu Jo; Gokhan Yilmaz; Sung Chun Tang; Aiwu Cheng; Marc Gleichmann; Eitan Okun; Vishwa D. Dixit; Srinivasulu Chigurupati; Mohamed R. Mughal; Xin Ouyang; Lucio Miele; Tim Magnus; Suresh Poosala; D. Neil Granger; Mark P. Mattson

doi:10.1038/nm1403

Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke

Thiruma V. Arumugam, Sic L. Chan, Dong Gyu Jo, Gokhan Yilmaz, Sung Chun Tang, Aiwu Cheng, Marc Gleichmann, Eitan Okun, Vishwa D. Dixit, Srinivasulu Chigurupati, Mohamed R. Mughal, Xin Ouyang, Lucio Miele, Tim Magnus, Suresh Poosala, D. Neil Granger, Mark P. Mattson

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229 Scopus citations

Abstract

Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme γ-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.

Original language	English
Pages (from-to)	621-623
Number of pages	3
Journal	Nature Medicine
Volume	12
Issue number	6
DOIs	https://doi.org/10.1038/nm1403
State	Published - Jun 2006
Externally published	Yes

Bibliographical note

Funding Information:
We thank H. Zhu for technical assistance and B. De Strooper for providing presenilin-deficient cells. This research was supported by the National Institute on Aging Intramural Research Program of the US National Institutes of Health.

Funding

We thank H. Zhu for technical assistance and B. De Strooper for providing presenilin-deficient cells. This research was supported by the National Institute on Aging Intramural Research Program of the US National Institutes of Health.

Funders	Funder number
National Institutes of Health
National Institute on Aging	ZIAAG000313

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Arumugam, T. V., Chan, S. L., Jo, D. G., Yilmaz, G., Tang, S. C., Cheng, A., Gleichmann, M., Okun, E., Dixit, V. D., Chigurupati, S., Mughal, M. R., Ouyang, X., Miele, L., Magnus, T., Poosala, S., Granger, D. N., & Mattson, M. P. (2006). Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke. Nature Medicine, 12(6), 621-623. https://doi.org/10.1038/nm1403

@article{fe795f16e00d450a80e56b202c77581c,

title = "Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke",

abstract = "Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme γ-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.",

author = "Arumugam, {Thiruma V.} and Chan, {Sic L.} and Jo, {Dong Gyu} and Gokhan Yilmaz and Tang, {Sung Chun} and Aiwu Cheng and Marc Gleichmann and Eitan Okun and Dixit, {Vishwa D.} and Srinivasulu Chigurupati and Mughal, {Mohamed R.} and Xin Ouyang and Lucio Miele and Tim Magnus and Suresh Poosala and Granger, {D. Neil} and Mattson, {Mark P.}",

note = "Funding Information: We thank H. Zhu for technical assistance and B. De Strooper for providing presenilin-deficient cells. This research was supported by the National Institute on Aging Intramural Research Program of the US National Institutes of Health.",

year = "2006",

month = jun,

doi = "10.1038/nm1403",

language = "אנגלית",

volume = "12",

pages = "621--623",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

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Arumugam, TV, Chan, SL, Jo, DG, Yilmaz, G, Tang, SC, Cheng, A, Gleichmann, M, Okun, E, Dixit, VD, Chigurupati, S, Mughal, MR, Ouyang, X, Miele, L, Magnus, T, Poosala, S, Granger, DN & Mattson, MP 2006, 'Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke', Nature Medicine, vol. 12, no. 6, pp. 621-623. https://doi.org/10.1038/nm1403

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T1 - Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke

AU - Arumugam, Thiruma V.

AU - Chan, Sic L.

AU - Jo, Dong Gyu

AU - Yilmaz, Gokhan

AU - Tang, Sung Chun

AU - Cheng, Aiwu

AU - Gleichmann, Marc

AU - Okun, Eitan

AU - Dixit, Vishwa D.

AU - Chigurupati, Srinivasulu

AU - Mughal, Mohamed R.

AU - Ouyang, Xin

AU - Miele, Lucio

AU - Magnus, Tim

AU - Poosala, Suresh

AU - Granger, D. Neil

AU - Mattson, Mark P.

N1 - Funding Information: We thank H. Zhu for technical assistance and B. De Strooper for providing presenilin-deficient cells. This research was supported by the National Institute on Aging Intramural Research Program of the US National Institutes of Health.

PY - 2006/6

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N2 - Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme γ-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.

AB - Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme γ-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.

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Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke

Abstract

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