Subcutaneous Nogo Receptor Removes Brain Amyloid-β and Improves Spatial Memory in Alzheimer's Transgenic Mice

Park, James H.; Widi, Gabriel; Gimbel, David A.; Harel, Noam Y.; Lee, Daniel H. S.; Strittmatter, Stephen M.

doi:10.1523/jneurosci.4504-06.2006

Cited by 100 publications

(95 citation statements)

References 45 publications

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“…Excessive expression of NgR has been shown to prevent α-and β-secretase from cleaving amyloid precursor protein (APP), which reduces the production of Aβ (Park, 2006b). Aβ/APP metabolism is a complex multi-step process involving a variety of proteins.…”

Section: Discussionmentioning

confidence: 99%

Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats

Yin¹,

Wang²,

Li³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Curcumin has been widely used for the prevention and treatment of Alzheimer's disease (AD), but its mechanism is still not clear. Inhibitory factors of axonal regeneration have been shown to cause a series of pathophysiological changes in the early period of AD. In this study, the co-receptor (Nogo receptor; NgR) of three axonal growth-inhibitory proteins was examined, and effects of curcumin on spatial learning and memory abilities and hippocampal axonal growth were investigated in amyloid β-protein (Aβ)1-40-induced AD rats. Results showed that the expression of NgR in the AD group significantly increased and the number of axonal protein-positive fibers significantly reduced. The spatial learning and memory abilities of AD rats were significantly improved in the curcumin group. Furthermore, hippocampal expressions of NgR mRNA and protein decreased, and the expression of axonal protein significantly increased. There was a negative correlation between the expression of NgR and axonal growth. Together, these results suggested that curcumin could improve the spatial learning and memory abilities of AD rats. The mechanism

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Section: Discussionmentioning

confidence: 99%

Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats

Yin¹,

Wang²,

Li³

et al. 2014

Genet. Mol. Res.

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“…Beyond its suggested role in SCI, NgR1 has been discussed to be involved in neurodegenerative diseases and to possess multiple physiological functions [48][49][50][51][52], for example including regulation of macrophage movement in inflammatory responses [31]. With respect to its involvement in neurodegenerative diseases it was demonstrated that NgR1 directly interacts with Aβ and APP.…”

Section: Relevance Of Ngr1 In Brain Physiology and Further Disease Inmentioning

confidence: 99%

“…With respect to its involvement in neurodegenerative diseases it was demonstrated that NgR1 directly interacts with Aβ and APP. Overexpression of NgR reduces plaque load, and also treatment of APPswe/PSEN-1ΔE9 transgenic mice with the decoy receptor NgR(310)ecto-Fc is able to reduce plaque load and leads to improved spatial memory in these animals [48,49]. In addition, NgR1 may be directly involved in plasticity and synaptic functioning [53,54] and a slower acquisition of a spatial learning and memory task has recently been described for NgR1 (-/-) mice [55].…”

Section: Relevance Of Ngr1 In Brain Physiology and Further Disease Inmentioning

confidence: 99%

Blocking Nogo Receptor 1 Promotes Functional Regeneration after Spinal Cord Injury

A¹,

AH²

2013

J Neurol Disord

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“…As Strittmatter outlined in his Keystone presentation, the laboratory had previously shown that the Nogo receptor, known for limiting axon regeneration and repair, binds to the AβPP and to Aβ, but not necessarily oligomers [3,4]. To find proteins that specifically bind to oligomeric species of the peptide, which are now widely believed to be the most toxic Aβ entities, Juha Lauren and colleagues in the laboratory used biotinlabeled oligomers (prepared as per the ADDL method of Bill Klein's group) [5] to screen COS-7 cells expressing a mouse adult brain cDNA library.…”

Section: Partners In Crime -Do Aβ and Prion Protein Pummel Plasticity?mentioning

confidence: 99%

Keystone Symposium, Neurodegenerative Diseases: New Molecular Mechanisms 17–22 February 2009

Fagan

2009

JAD

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On Wednesday of the meeting, debate over the last plenary talk continued around the dinner table and well into the poster session. Marc Tessier-Lavigne, Genentech Inc., San Francisco, California, described a novel role for amyloid-β protein precursor (AβPP) in neurodegeneration, a role that appears completely independent of amyloid-β (Aβ) toxicity and that might finally explain why only certain neurons bear the brunt of Alzheimer's disease (AD) pathology. Tessier-Lavigne reported that the extracellular domain of AβPP serves as a ligand for death receptor 6 (DR6), an orphan member of the tumor necrosis factor receptor superfamily. He showed that when the N-terminus of AβPP (N-AβPP) binds DR6, it sets off an apoptotic cascade in embryonic spinal neurons that targets both axons and cell bodies. The work indicates that N-AβPP has a role in axonal pruning and neural cell death in development, but it also raises the possibility that similar events occur in mature neurons in the brain. "Finding that an N-terminal fragment of AβPP is a ligand for DR6 came as a complete surprise, and finding that AβPP is involved in a self-destruction mechanism like this immediately suggested that perhaps it could contribute to Alzheimer's disease," said Tessier-Lavigne in an interview with this reporter after the talk. The study was coincidentally published in Wednesday's Nature. "This is very intriguing. I think the story is very convincing because there is a lot of very complementary data, biochemical, cell biological, etc., and I do not doubt that it is relevant for AβPP biology," said Bart De Strooper, University of Leuven, Belgium, who was at the meeting. He was not involved in the study. "Of course, when you have this type of data I think it is fair to ask how relevant it is for Alzheimer's disease. I think it is too early to say if it is equivalent to the amyloid hypothesis, for example, because there is no human or clinical data," he cautioned.Tessier-Lavigne and colleagues identified the N-AβPP/DR6 interaction when studying neuronal development. The embryo is a tough environment for new neurons with many more being formed than typically needed. Those that do not make proper connections are eventually weeded out by a process that involves axonal pruning and cell death. First author Anatoly Nikolaev and colleagues found that DR6 plays a key role in this process, kicking off an apoptotic pathway in commissural, motor, and sensory neurons that depends on activation of caspase 6 in axons and caspase 3 in the soma only [1]. Nikolaev and colleagues mimicked this axon degeneration by withdrawing trophic support (such as nerve growth factor, or NGF) from neurons in culture, but if they blocked DR6 at the same time -with an antibody, by knocking it down with RNAi, or by genetic knockout -they were able to prevent axonopathy and cell death. Collaborating with Todd McLaughlin and Dennis O'Leary at the Salk Institute, they also showed that DR6 regulates neuron death and axonal pruning not just in cell culture, but also in vivo in a mouse mod...

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Subcutaneous Nogo Receptor Removes Brain Amyloid-β and Improves Spatial Memory in Alzheimer's Transgenic Mice

Cited by 100 publications

References 45 publications

Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats

Effects of curcumin on hippocampal expression of NgR and axonal regeneration in Aβ-induced cognitive disorder rats

Blocking Nogo Receptor 1 Promotes Functional Regeneration after Spinal Cord Injury

Keystone Symposium, Neurodegenerative Diseases: New Molecular Mechanisms 17–22 February 2009

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