Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice.
One aspect of Alzheimer's disease is the existence of dystrophic neurites in and near Amyloid β (Aβ) plaques. In previous work, we have shown that Nogo-66 Receptor (NgR)regulates axonal sprouting and regeneration in the adult central nervous system. Therefore, we have investigated whether the NgR pathway titrates the dystrophic neurite response in Alzheimer's disease. Unexpectedly, we found a direct interaction between APP and NgR that alters Aβ processing upstream of a downstream dystrophic response to Aβ peptide deposition. We examined the effect of NgR on Aβ accumulation in vivo. Deletion of NgR expression increases Aβ plaque deposition in transgenic mice, while excess soluble NgR treatment reduces Aβ plaque deposition in mice. The potential mechanistic bases for NgR modification of the Alzheimer's disease are discussed [corrected].
Park
James H
JH
Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
Strittmatter
Stephen M
SM
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D018000:Receptors, Peptide / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D018000:Receptors, Peptide