QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 20, 2006, 26(51):13279-13286; doi:10.1523/JNEUROSCI.4504-06.2006

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Park, J. H. Articles by Strittmatter, S. M. Search for Related Content PubMed PubMed Citation Articles by Park, J. H. Articles by Strittmatter, S. M.

 Previous Article  |  Next Article 

Neurobiology of Disease
Subcutaneous Nogo Receptor Removes Brain Amyloid-ß and Improves Spatial Memory in Alzheimer's Transgenic Mice

James H. Park,¹ Gabriel A. Widi,¹ David A. Gimbel,¹ Noam Y. Harel,¹ Daniel H. S. Lee,² and Stephen M. Strittmatter¹

¹Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, Connecticut 06510, and ²Biogen Idec, Cambridge, Massachusetts 02140

Correspondence should be addressed to Stephen M. Strittmatter, Department of Neurology, Yale University School of Medicine, P.O. Box 208018, New Haven, CT 06510. Email: stephen.strittmatter{at}yale.edu

The production and aggregation of cerebral amyloid-ß (Aß) peptide are thought to play a causal role in Alzheimer's disease (AD). Previously, we found that the Nogo-66 receptor (NgR) interacts physically with both Aß and the amyloid precursor protein (APP). The inverse correlation of Aß levels with NgR levels within the brain may reflect regulation of Aß production and/or Aß clearance. Here, we assess the potential therapeutic benefit of peripheral NgR-mediated Aß clearance in APPswe/PSEN-1E9 transgenic mice. Through site-directed mutagenesis, we demonstrate that the central 15–28 aa of Aß associate with specific surface-accessible patches on the leucine-rich repeat concave side of the solenoid structure of NgR. In transgenic mice, subcutaneous NgR(310)ecto-Fc treatment reduces brain Aß plaque load while increasing the relative levels of serum Aß. These changes in Aß are correlated with improved spatial memory in the radial arm water maze. The benefits of peripheral NgR administration are evident when therapy is initiated after disease onset. Thus, the peripheral association of NgR(310)ecto-Fc with central Aß residues provides an effective therapeutic approach for AD.

Key words: Alzheimer's disease; ß-amyloid; Nogo-66 receptor; axon; therapy; radial arm water maze; degeneration; amyloid precursor protein

---

Received Aug. 10, 2006; accepted Nov. 12, 2006.

Correspondence should be addressed to Stephen M. Strittmatter, Department of Neurology, Yale University School of Medicine, P.O. Box 208018, New Haven, CT 06510. Email: stephen.strittmatter{at}yale.edu

This article has been cited by other articles:

				Y. Zou Axons find their way in the snow Development, July 1, 2009; 136(13): 2135 - 2139. [Abstract] [Full Text] [PDF]

				S. Budel, T. Padukkavidana, B. P. Liu, Z. Feng, F. Hu, S. Johnson, J. Lauren, J. H. Park, A. W. McGee, J. Liao, et al. Genetic Variants of Nogo-66 Receptor with Possible Association to Schizophrenia Block Myelin Inhibition of Axon Growth J. Neurosci., December 3, 2008; 28(49): 13161 - 13172. [Abstract] [Full Text] [PDF]

				Y. Bai, K. Markham, F. Chen, R. Weerasekera, J. Watts, P. Horne, Y. Wakutani, R. Bagshaw, P. M. Mathews, P. E. Fraser, et al. The in Vivo Brain Interactome of the Amyloid Precursor Protein Mol. Cell. Proteomics, January 1, 2008; 7(1): 15 - 34. [Abstract] [Full Text] [PDF]

				S. Petratos, Q.-X. Li, A. J. George, X. Hou, M. L. Kerr, S. E. Unabia, I. Hatzinisiriou, D. Maksel, M.-I. Aguilar, and D. H. Small The -amyloid protein of Alzheimer's disease increases neuronal CRMP-2 phosphorylation by a Rho-GTP mechanism Brain, January 1, 2008; 131(1): 90 - 108. [Abstract] [Full Text] [PDF]

				Disease Mechanisms in Neuroscience Neuroscientist, June 1, 2007; 13(3): 198 - 198. [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help