Intrathecally infused antibodies against Nogo-A penetrate the CNS and downregulate the endogenous neurite growth inhibitor Nogo-A

Weinmann, Oliver; Schnell, Lisa; Ghosh, Arko; Montani, Laura; Wiessner, Christoph; Wannier, Thierry; Rouiller, Eric M.; Mir, Anis K.

doi:10.1016/j.mcn.2006.03.007

Cited by 77 publications

(60 citation statements)

References 55 publications

(86 reference statements)

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“…Many peripheral and central neurons express Nogo-A in development but downregulate the protein to low or undetectable levels after birth (Huber et al, 2002). Antibodies were found intracellularly, internalized together with endogenous Nogo-A in endosomes and lysosomes (Weinmann et al, 2006). In accordance with these findings, the overall Nogo-A levels as determined by immunoblots and immunofluorescence were decreased in CNS tissues exposed to antibodies in vivo.…”

Section: The Physiological Roles Of Myelin-associated Inhibitory Protsupporting

confidence: 68%

“…An important observation was that antibodies against Nogo-A infused into the lumbar CSF space by a pump linked to an intrathecal catheter for 7 d reached the entire spinal cord and large parts of the brain in adult rats as well as adult macaque monkeys (Weinmann et al, 2006). These antibodies were retained in the tissues by binding to surface Nogo-A in white matter, on oligodendrocytes, and also on a subpopulations of neurons expressing Nogo-A throughout life.…”

Section: The Physiological Roles Of Myelin-associated Inhibitory Protmentioning

confidence: 99%

See 1 more Smart Citation

Spinal Cord Injury: Time to Move?

Rossignol

Schwab²,

Schwartz³

et al. 2007

J. Neurosci.

258

170

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This symposium aims at summarizing some of the scientific bases for current or planned clinical trials in patients with spinal cord injury (SCI). It stems from the interactions of four researchers involved in basic and clinical research who presented their work at a dedicated Symposium of the Society for Neuroscience in San Diego. After SCI, primary and secondary damage occurs and several endogenous processes are triggered that may foster or hinder axonal reconnection from supralesional structures. Studies in animals show that some of these processes can be enhanced or decreased by exogenous interventions using drugs to diminish repulsive barriers (anti-Nogo, anti-Rho) that prevent regeneration and/or sprouting of axons. Cell grafts are also envisaged to enhance beneficial immunological mechanisms (autologous macrophages, vaccines) or remyelinate axons (oligodendrocytes derived from stem cells). Some of these treatments could be planned concurrently with neurosurgical approaches that are themselves beneficial to decrease secondary damage (e.g., decompression/reconstructive spinal surgery). Finally, rehabilitative approaches based on the presence of functional networks (i.e., central pattern generator) below the lesion combined with the above neurobiological approaches may produce significant functional recovery of some sensorimotor functions, such as locomotion, by ensuring an optimal function of endogenous spinal networks and establishing new dynamic interactions with supralesional structures. More work is needed on all fronts, but already the results offer great hope for functional recovery after SCI based on sound basic and clinical neuroscience research.

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Section: The Physiological Roles Of Myelin-associated Inhibitory Protsupporting

confidence: 68%

Section: The Physiological Roles Of Myelin-associated Inhibitory Protmentioning

confidence: 99%

Spinal Cord Injury: Time to Move?

Rossignol

Schwab²,

Schwartz³

et al. 2007

J. Neurosci.

258

170

View full text Add to dashboard Cite

show abstract

“…However, no experimental evidence demonstrates that aminoNogo-A can release from oligodendrocyte surface. As to the in vivo results, the facts that pretreatment of antibody 11C7 is internalized into intracellular vacuoles of neurons 31,33 and neuronal Nogo-A knockout simultaneously occurs in Nogo-Adeficient mice 31 support the concept that neuronal Nogo-A may participate in cell survival against oxidative stress in the ischemic model mice. In the future, construction of neuronalspecific knockout mice of Nogo-A or Nogo-A/B or transgenic mice of amino-Nogo-A, especially the domain of aa 290-562, will hopefully help to clarify these issues.…”

Section: Discussionmentioning

confidence: 73%

Amino-Nogo-A antagonizes reactive oxygen species generation and protects immature primary cortical neurons from oxidative toxicity

Hou

et al. 2012

Cell Death Differ

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Nogo-A is originally identified as an inhibitor of axon regeneration from the CNS myelin. Nogo-A is mainly expressed by oligodendrocytes, and also by some neuronal subpopulations, particularly in the developing nervous system. Although extensive studies have uncovered regulatory roles of Nogo-A in neurite outgrowth inhibition, precursor migration, neuronal homeostasis, plasticity and neurodegeneration, its cell-autonomous functions in neurons are largely uncharacterized. Here, we show that HIV-1 trans-activating-mediated amino-Nogo-A protein transduction into cultured primary cortical neurons achieves an almost complete neuroprotection against oxidative stress induced by exogenous hydrogen peroxide (H 2 O 2 ). Endogenously expressed neuronal Nogo-A is significantly downregulated upon H 2 O 2 treatment. Furthermore, knockdown of Nogo-A results in more susceptibility to acute oxidative insults and markedly increases neuronal death. Interacting with peroxiredoxin 2 (Prdx2), amino-Nogo-A reduces reactive oxygen species (ROS) generation and extracellular signal-regulated kinase phosphorylation to exert neuroprotective effects. Structure-function mapping experiments reveal that, out of NiG-D20, a novel region comprising residues 290-562 of amino-Nogo-A is indispensable for preventing oxidative neuronal death. Moreover, mutagenesis analysis confirms that cysteine residues 424, 464 and 559 are involved in the inhibition of ROS generation and neuroprotective role of amino-Nogo-A. Our data suggest that neuronal Nogo-A might play a cell-autonomous role in improving neuronal survival against oxidative insult through interacting with Prdx2 and scavenging of ROS.

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“…The second antibody used, mAb hNogo-A recognized the Nogo-A specific region of the human Nogo-A sequence. Both antibodies identify primate Nogo-A monospecifically on Western blots (Freund et al, , 2007Oertle et al, 2003;Weinmann et al, 2006). The antibodies were purified as IgGs and concentrated to 3.7-10 mg/ml in PBS (Freund et al, 2007).…”

Section: Anti-nogo-a Antibodiesmentioning

confidence: 99%

Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: Effects of an antibody treatment neutralizing Nogo-A

et al. 2008

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The present study describes in primates the effects of a spinal cord injury on the number and size of the neurons in the magnocellular part of the red nucleus (RNm), the origin of the rubrospinal tract, and evaluates whether a neutralization of Nogo-A reduces the lesionedinduced degenerative processes observed in RNm. Two groups of monkeys were subjected to unilateral section of the spinal cord affecting the rubrospinal tract; one group was subsequently treated with an antibody neutralizing Nogo-A; the second group received a control antibody. Intact animals were also included in the study. Counting neurons stained with a monoclonal antibody recognizing non-phosphorylated epitopes on neurofilaments (SMI-32) indicated that their number in the contralesional RNm was consistently inferior to that in the ipsilesional RNm, in a proportion amounting up to 35%. The lesion also induced shrinkage of the soma of the neurons detected in the contralesional RNm. Infusing an antiNogo-A antibody at the site of the lesion did not increase the proportion of SMI-32 positive rubrospinal neurons in the contralesional RNm nor prevent shrinkage.

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Intrathecally infused antibodies against Nogo-A penetrate the CNS and downregulate the endogenous neurite growth inhibitor Nogo-A

Cited by 77 publications

References 55 publications

Spinal Cord Injury: Time to Move?

Spinal Cord Injury: Time to Move?

Amino-Nogo-A antagonizes reactive oxygen species generation and protects immature primary cortical neurons from oxidative toxicity

Fate of rubrospinal neurons after unilateral section of the cervical spinal cord in adult macaque monkeys: Effects of an antibody treatment neutralizing Nogo-A

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