Abstract
Pathophysiologic hypotheses for Alzheimers disease (AD) are centered on the role of the amyloid plaque Aβ peptide and the mechanism of its derivation from the amyloid precursor protein (APP). As part of the disease process, an aberrant axonal sprouting response is known to occur near Aβ deposits. A Nogo to Nogo-66 receptor (NgR) pathway contributes to determining the ability of adult CNS axons to extend after traumatic injuries. Here, we consider the potential role of NgR mechanisms in AD. Both Nogo and NgR are mislocalized in AD brain samples. APP physically associates with the NgR. Overexpression of NgR decreases Aβ production in neuroblastoma culture, and targeted disruption of NgR expression increases transgenic mouse brain Aβ levels, plaque deposition, and dystrophic neurites. Infusion of a soluble NgR fragment reduces Aβ levels, amyloid plaque deposits, and dystrophic neurites in a mouse transgenic AD model. Changes in NgR level produce parallel changes in secreted APP and AB, implicating NgR as a blocker of secretase processing of APP. The NgR provides a novel site for modifying the course of AD and highlights the role of axonal dysfunction in the disease.
Keywords: Alzheimers pathology, Amyloid plaque, neuritic dystrophy, APP trafficking, Nogo-A
Current Alzheimer Research
Title: Nogo Receptor Interacts with Brain APP and Aβ to Reduce Pathologic Changes in Alzheimers Transgenic Mice
Volume: 4 Issue: 5
Author(s): James H. Park and Stephen M. Strittmatter
Affiliation:
Keywords: Alzheimers pathology, Amyloid plaque, neuritic dystrophy, APP trafficking, Nogo-A
Abstract: Pathophysiologic hypotheses for Alzheimers disease (AD) are centered on the role of the amyloid plaque Aβ peptide and the mechanism of its derivation from the amyloid precursor protein (APP). As part of the disease process, an aberrant axonal sprouting response is known to occur near Aβ deposits. A Nogo to Nogo-66 receptor (NgR) pathway contributes to determining the ability of adult CNS axons to extend after traumatic injuries. Here, we consider the potential role of NgR mechanisms in AD. Both Nogo and NgR are mislocalized in AD brain samples. APP physically associates with the NgR. Overexpression of NgR decreases Aβ production in neuroblastoma culture, and targeted disruption of NgR expression increases transgenic mouse brain Aβ levels, plaque deposition, and dystrophic neurites. Infusion of a soluble NgR fragment reduces Aβ levels, amyloid plaque deposits, and dystrophic neurites in a mouse transgenic AD model. Changes in NgR level produce parallel changes in secreted APP and AB, implicating NgR as a blocker of secretase processing of APP. The NgR provides a novel site for modifying the course of AD and highlights the role of axonal dysfunction in the disease.
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Cite this article as:
Park H. James and Strittmatter M. Stephen, Nogo Receptor Interacts with Brain APP and Aβ to Reduce Pathologic Changes in Alzheimers Transgenic Mice, Current Alzheimer Research 2007; 4 (5) . https://dx.doi.org/10.2174/156720507783018235
DOI https://dx.doi.org/10.2174/156720507783018235 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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