Back to Search
Start Over
Subcutaneous Nogo receptor removes brain amyloid-beta and improves spatial memory in Alzheimer's transgenic mice.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2006 Dec 20; Vol. 26 (51), pp. 13279-86. - Publication Year :
- 2006
-
Abstract
- The production and aggregation of cerebral amyloid-beta (Abeta) 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 Abeta and the amyloid precursor protein (APP). The inverse correlation of Abeta levels with NgR levels within the brain may reflect regulation of Abeta production and/or Abeta clearance. Here, we assess the potential therapeutic benefit of peripheral NgR-mediated Abeta clearance in APPswe/PSEN-1deltaE9 transgenic mice. Through site-directed mutagenesis, we demonstrate that the central 15-28 aa of Abeta 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 Abeta plaque load while increasing the relative levels of serum Abeta. These changes in Abeta 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 Abeta residues provides an effective therapeutic approach for AD.
- Subjects :
- Alzheimer Disease therapy
Amyloid beta-Peptides antagonists & inhibitors
Animals
Brain physiology
COS Cells
Chlorocebus aethiops
GPI-Linked Proteins
Humans
Injections, Subcutaneous
Mice
Mice, Transgenic
Myelin Proteins administration & dosage
Myelin Proteins metabolism
Nogo Receptor 1
Protein Binding physiology
Rats
Receptors, Cell Surface administration & dosage
Receptors, Cell Surface metabolism
Alzheimer Disease metabolism
Amyloid beta-Peptides metabolism
Brain metabolism
Memory physiology
Myelin Proteins physiology
Receptors, Cell Surface physiology
Spatial Behavior physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 26
- Issue :
- 51
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 17182778
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.4504-06.2006