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p75NTR Antagonistic Cyclic Peptide Decreases the Size of β Amyloid-Induced Brain Inflammation

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Abstract

Amyloid beta (Aβ) was shown to bind the 75 kD neurotrophin receptor (p75NTR) to induce neuronal death. We synthesized a p75NTR antagonistic peptide (CATDIKGAEC) that contains the KGA motif that is present in the toxic part of Aβ and closely resembles the binding site of NGF for p75NTR. In vivo injections of Aβ into the cerebral cortex of B57BL/6 mice together with the peptide produced significantly less inflammation than simultaneous injections of Aβ and a control (CKETIADGAC, scrambled) peptide injected into the contralateral cortex. These data suggest that blocking the binding of Aβ to p75NTR may reduce neuronal loss in Alzheimer’s disease.

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Acknowledgment

This work was supported by pilot grant from the Massachusetts Alzheimer’s Disease Research Center and from Boston University Community Technology Fund (MY) and the Department of Veteran’s Affairs, Department of Defense (98228055), and NIH (AG13846, AG12922) (NWK).

Conflict of Interest Statement

Aspects of the work reported in this correspondence pertain to patents for which M.Y. and B.A.G. are co-inventors. These patents are assigned to the Trustees of Boston University (their employer) and licensed to SemaCo, Inc., a for-profit company in which M.Y. and B.A.G. hold equity, created to commercialize intellectual property arising out of their laboratory.

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Authors and Affiliations

  1. Department of Dermatology, Boston University School of Medicine, 715 Albany Street, Boston, MA, 02118, USA

    Mina Yaar, Bennet L. Arble, Kenneth B. Stewart & Barbara A. Gilchrest

  2. Department of Pathology, Boston University School of Medicine, 715 Albany Street, Boston, MA, 02118, USA

    Mina Yaar & Neil W. Kowall

  3. Department of Veterans Affairs, Geriatric Research Education and Clinical Center, VA Medical Center, 200 Springs Road, Bedford, MA, 01730, USA

    Nazer H. Qureshi & Neil W. Kowall

  4. Department of Neurology, Boston University School of Medicine, 715 Albany Street, Boston, MA, 02118, USA

    Neil W. Kowall

  5. Department of Pathology, Boston University School of Medicine, 609 Albany Street, J-Building, Boston, MA, 02118-2394, USA

    Barbara A. Gilchrest

Authors
  1. Mina Yaar
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  2. Bennet L. Arble
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  3. Kenneth B. Stewart
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  4. Nazer H. Qureshi
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  5. Neil W. Kowall
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  6. Barbara A. Gilchrest
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Correspondence to Barbara A. Gilchrest.

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Yaar, M., Arble, B.L., Stewart, K.B. et al. p75NTR Antagonistic Cyclic Peptide Decreases the Size of β Amyloid-Induced Brain Inflammation. Cell Mol Neurobiol 28, 1027–1031 (2008). https://doi.org/10.1007/s10571-008-9298-6

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  • DOI: https://doi.org/10.1007/s10571-008-9298-6

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