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Repairing The Brain

neurogenesis bdnf neurod1 nogo stroke narcolepsy

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#1 Pereise1

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Posted 08 April 2017 - 03:55 PM

Hello all, so after researching like a law student these last couple months, I think I have an idea on how it might be possible to repair a CNS glial scar. There's many variables naturally, but I'm curious if this approach seems right to everyone here. If so, it'd be exciting to see what help it could be for someone with TBI or MS. I posted the following to the Narcolepsy Network forums:



Now, it's known that after a traumatic brain injury (TBI) or a stroke, reactive gliosis by glial cells in the brain cause a glial scar to form. Evidence of this happening is detailed in the following studies:
https://www.ncbi.nlm...les/PMC2717206/ (Localized Loss of Hypocretin (Orexin) Cells in Narcolepsy Without Cataplexy)
https://www.uptodate...lts/abstract/57 (Pattern of hypocretin (orexin) soma and axon loss, and gliosis, in human narcolepsy)
Herein lies the hard part and the reason Narcolepsy is so hard to treat and solve. When a glial scar is formed in the Central Nervous System (CNS) or spinal cord, it forms a lining that resists axon growth. Therefore, without intervention, the scar would be permanent, and no amount of neurogenesis inducing substances would be able to penetrate the glial scar. However, research in this field has accelerated highly in recent years, and there is hope. 
The brain uses different growth factors such as BDNF, NGF, GDNF, NT3, and CNTF to extend dendritic branching and axons. The goal is to use these to grow new orexin neurons over the scar tissue in the hypothalamus, and/or convert the glial cells into functioning neurons. The glial scar has a number of ways that it inhibits growth. It's a little too complicated to go into too much detail, but I'll include a few main ones as well as links to a number of studies at the bottom.
1. Modification of sulphated proteoglycans
What are these you may ask? I'm going to quote extensively from the study "Regeneration Beyond The Glial Scar" (http://www.nature.co...ll/nrn1326.html). To start:
In addition to growth-promoting molecules46, 47, astrocytes produce a class of molecules known as proteoglycans48, 49. These ECM molecules consist of a protein core linked by four sugar moieties to a sulphated GLYCOSAMINOGLYCAN (GAG) chain that contains repeating disaccharide units. Astrocytes produce four classes of proteoglycan; heparan sulphate proteoglycan (HSPG), dermatan sulphate proteoglycan (DSPG), keratan sulphate proteoglycan (KSPG) and chondroitin sulphate proteoglycan (CSPG)50. The CSPGs form a relatively large family, which includes aggrecan, brevican, neurocan, NG2, phosphacan (sometimes classed as a KSPG) and versican, all of which have chondroitin sulphate side chains. They differ in the protein core, as well as the number, length and pattern of sulphation of the side chains51, 52, 53. Expression of these CSPGs increases in the glial scar in the brain and spinal cord of mature animals54, 55, 56.
Proteoglycans have been implicated as barriers to CNS axon extension in the developing roof plate of the spinal cord57, 58, in the midline of the rhombencephalon and mesencephalon59, 60, at the dorsal root entry zone (DREZ)61, in retinal pattern development62, 63, and at the optic chiasm and distal optic tract64, 65. Extensive work has demonstrated that CSPGs are extremely inhibitory to axon outgrowth in culture. Neurites growing on alternating stripes of laminin and laminin/aggrecan had robust outgrowth on laminin, but at the sharp interface between the two surfaces, growth cones rapidly turned away (unlike their stalled behaviour in a gradient, see above). The inhibitory nature of the proteoglycan-containing lanes can repel embryonic as well as adult axons, and the effect can last for more than a week in vitro. The turning behaviour is not usually mediated by collapse of the entire growth cone, but rather by selective retraction of FILOPODIA in contact with CSPG and enhanced motility of those on laminin66, 67. CSPGs are potent inhibitors of a wide variety of other growth-promoting molecules, including fibronectin and L1 (Refs 68,69).
This is one of the most important steps to overcome. In the same study, it has been shown that, and I quote, "chondroitinase — an enzyme extracted from the bacterium Proteus vulgaris that selectively removes a large portion of the CSPG GAG side chain and renders CSPGs less inhibitory". Now, unfortunately I don't know where to get chondroitinase, if it passes the BBB, or how to guide it to the hypothalamus. However, after scouring pubmed for hours to find a replacement, I found good ol' Turmeric helps here:
Curcumin improves neural function after spinal cord injury by the joint inhibition of the intracellular and extracellular components of glial scar
We found that cur inhibited the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and NF-κb; reduced the expression of the intracellular components glial fibrillary acidic protein through anti-inflammation; and suppressed the reactive gliosis. Also, cur inhibited the generation of TGF-β1, TGF-β2, and SOX-9; decreased the deposition of chondroitin sulfate proteoglycan by inhibiting the transforming growth factors and transcription factor; and improved the microenvironment for nerve growth. Through the joint inhibition of the intracellular and extracellular components of glial scar, cur significantly reduced glial scar volume and improved the Basso, Beattie, and Bresnahan locomotor rating and axon growth.
Turmeric also has HDAC inhibiting properties, making the brain more malleable to change and encouraging it to return to homeostasis. I won't go too deep into HDAC but it seems to help.
2. Blocking the effects of myelin
Again, what's this and what would it do? Here's another citation from the same article:
In addition to enhancing regeneration by removing the inhibitory effects of CSPGs, extensive work has shown that blocking Nogo, a myelin-associated inhibitor of regeneration, improves regeneration105. Antibodies directed against the Nogo receptor administered into spinal cord lesion sites106 or even systemically107 seem to enhance regeneration, although recent work108 has disputed whether this is truly enhanced regeneration or merely local sprouting. Indeed, it is now being suggested that most of the functional recovery that is seen when inhibitors of myelin are used occurs as a result of remodelling of local circuits, such that functional recovery is mediated along uninjured long axons108. This proposal, in conjunction with work from our laboratory demonstrating rapid axon regrowth from adult neurons in the presence of degenerating white matter83, 84, as well as the differences between growth cone collapse and dystrophy, indicates that myelin might not be acting fundamentally to inhibit long-distance regeneration. In fact, it has even been suggested that myelin might facilitate axon growth under certain conditions109.
So how do we get around this issue? Here, we turn to Longecity and the amazing research of some of users there (http://www.longecity...th/#entry737252). To cite only 2 studies, Ginseng and Horny Goat Weed (Icariin) are potent in this regard:
We determined 1) GTS (Ginsenoides) (5-80 mg/kg) treatment after a TBI improved the recovery of neurological functions, including learning and memory, and reduced cell loss in the hippocampal area. The effects of GTS at 20, 40, 60, and 80 mg/kg were better than the effects of GTS at 5 and 10 mg/kg. 2) GTS treatment (20 mg/kg) after a TBI increased the expression of NGF, GDNF and NCAM, inhibited the expression of Nogo-A, Nogo-B, TN-C, and increased the number of BrdU/nestin positive NSCs in the hippocampal formation.
Icariin, the major active component of Chinese medicinal herb epimedium brevicornum maxim, is used widely in traditional Chinese medicine for the treatment of neurological diseases. However, the effects of icariin on myelin inhibitory factors are as yet unclear. In the present study, administration of icariin at 20 mg/kg showed a marked reduction in neurological deficit of middle cerebral artery occlusion rats. Icariin exhibited better inhibitory effects on myelin inhibitory factors: Nogo-A, myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein in ischemia regions of middle cerebral artery occlusion rats compared with monosialotetrahexosylganglioside. These results indicate that icariin exhibits potent inhibitory effects on expression of myelin inhibitors after middle cerebral artery occlusion-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both Nogo-A, myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein activation, followed by the enhancement of axonal sprouting and regeneration, resulting in neurological functional...
Seems Nogo is among the easier things to inhibit, thankfully.
3. Enhancing the intrinsic growth machinery.
This is pretty straightforward, we want the best environment for these new axons to differentiate and turn into full neurons:
Removal of extrinsic inhibitory cues from the glial scar with treatments such as chondroitinase might aid regeneration, but this might not be sufficient for long-range re-growth. Neurotrophin 3 (NT3) or nerve growth factor (NGF), when delivered directly to transected neurons in the dorsal columns of animals treated with peripheral nerve graft transplants, enhances growth into the graft, out the opposite end and beyond the glial scar into host tissue110, 111. Exogenous NGF administration also induces sprouting into the lesion of crushed dorsal columns112. Intrathecal or adenoviral application of NT3 or NGF to the injured DREZ induces DRG neurons to cross the peripheral nervous system/CNS barrier and penetrate some distance into the spinal cord113, 114, 115, 116, 117, where the regenerating fibres restore nocioceptive function. So, evidence from the injured spinal cord and DREZ indicates that regenerating axons can overcome proteoglycan barriers after neurotrophin stimulation, perhaps through induction of growth enhancing genes, offering an additional therapeutic strategy.
As for Nerve Growth Factor, there's myriad things that stimulate this, so whatever you decide to take, make sure you enhance it with Acetyl L-Carnitine, which is supposed to enhance NGF by x100 according to a study I've recently misplaced. As for Neurotrophin 3, again, we have some amazing phytoconstituents to help. Another Longecity thread (http://www.longecity...s-into-neurons/) helped me find studies for 2 substances in particular, Chinese Skullcap and Ziziphus Jujube:
Baicalin promotes neuronal differentiation of neural stem/progenitor cells through modulating p-stat3 and bHLH family protein expression.
Signal transducer and activator of transcription 3 (stat3) and basic helix-loop-helix (bHLH) gene family are important cellular signal molecules for the regulation of cell fate decision and neuronal differentiation of neural stem/progenitor cells (NPCs). In the present study, we investigated the effects of baicalin, a flavonoid compound isolated from Scutellaria baicalensis G, on regulating phosphorylation of stat3 and expression of bHLH family proteins and promoting neuronal differentiation of NPCs. Embryonic NPCs from the cortex of E15-16 rats were treated with baicalin (2, 20 μM) for 2h and 7 days. Neuronal and glial differentiations were identified with mature neuronal marker microtubule associated protein (MAP-2) and glial marker Glial fibrillary acidic protein (GFAP) immunostaining fluorescent microscopy respectively. Phosphorylation of stat3 (p-stat3) and expressions of bHLH family genes including Mash1, Hes1 and NeuroD1 were detected with immunofluorescent microscopy and Western blot analysis. The results revealed that baicalin treatment increased the percentages of MAP-2 positive staining cells and decreased GFAP staining cells. Meanwhile, baicalin treatment down-regulated the expression of p-stat3 and Hes1, but up-regulated the expressions of NeuroD1 and Mash1. Those results indicate that baicalin can promote the neural differentiation but inhibit glial formation and its neurogenesis-promoting effects are associated with the modulations of stat3 and bHLH genes in neural stem/progenitor cells.
The treatment with jujube water extract stimulated the expressions of neurotrophic factors in a dose-dependent manner, with the highest induction of ~100% for NGF, 100% for brain-derived neurotrophic factor (BDNF), 100% for glial cell line-derived neurotrophic factor (GDNF) and 50% for neurotrophin 3 (NT3). These results supported the neurotrophic role of jujube on the brain.
Now, I have no idea how long it would take, under ideal circumstances, for the brain to regrow orexin neurons after disinhibiting growth and inducing axon growth in this manner. Any help understanding the process behind regrowing the hypothalamus and guiding growth to this section of the brain would be much appreciated. In the meantime, I leave everyone with some studies:
https://www.ncbi.nlm...les/PMC2693386/ (Glial inhibition of CNS axon regeneration)
https://www.ncbi.nlm...les/PMC3140701/ (Enhancing Central Nervous System Repair-The Challenges)
http://www.nature.co...ll/nrn1326.html (Regeneration Beyond The Glial Scar)
Also, these longecity threads helped me find a few relevant studies as well as substances to help neurogenesis:

#2 monowav

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Posted 10 April 2017 - 11:09 PM

Since you've mentioned it a lot, here's all my info on nogo-A.



Reticulon 4 Is More Than A Growth Inhibitor

Nogo-A is one of the most potent growth inhibitors in the central nervous system. It is involved in creating new blood cells, developing new stem cells, protecting growth of cancer, and modulating the immune system. It is highly expressed after adolescent development, traumatic brain injuries, and many myelin-related diseases. 








Schwab and Caroni discovered that myelin (the fatty white substance that surrounds the axon of some nerve cells) from the central nervous system (CNS) inhibits neurite outgrowth. R

Myelin from the peripheral nervous system (PNS) does the opposite. R

In the human brain, the growth of myelin is regulated by multiple systems: 

  • oligodendrocyte-myelin glycoprotein (OMgp) R
  • the reticulon RTN4 (Nogo) R
  • semaphorins R
  • ephrins R
  • chondroitin sulphate proteoglycans R

When Nogo-A is active, it acts as a myelin-derived neurite and axon growth inhibitor. R

It suppresses growth and sprouting of neurons, thus stabilizing the wiring of the adult CNS. R

It does this by regulating axonal and neural stem cells and progenitor cells. R R

Nogo-A can also inhibit the neuronal benefits of brain derived neurotrophic factor (BDNF). R

Nogo-A And Cell Functioning

Nogo-A is involved with normal cell-functioning, along with neuropsychiatric functions. R R

It helps regulate cell death and/or growth mechanisms. R

Nogo-A can protect against hydrogen peroxide-induced cell death. R

It does this by interacting with the enzyme peroxiredoxin 2, which scavenges reactive oxygen species (ROS). R

Nogo-A is upregulated in many cells as an inhibitory factor on the growth of tumor cells, helping prevent the spread of cancer. R

Nogo-A And Injury

After injury NgR (Nogo receptors) increase. R

Nogo-A increases in the cell body of injured neurons. R

It restricts axonal regeneration after injury. R

Nogo-A In The Brain

Nogo-A is expressed in neurons throughout the brain and spinal cord (and also oligodendrocytes). R

In humans, Nogo-A has been detected in the spinal cord, in the hippocampus, in the cerebral cortex, in the cerebellum and in the brain stem. R

Neuronal Nogo-A is highly expressed during ages of development and down-regulated when we are adults (from birth to adolescence, it is expressed in different areas of the brain and in adulthood it is expressed more in the cerebral cortex). R R

Nogo-A expression helps the development of immature neurons before myelination. R

After myelination, Nogo-A expression is stays high in plastic CNS regions such as the hippocampus, olfactory bulb, deep cerebellar nuclei, spinal motor neurons, and dorsal root ganglia. R R

Nogo-A and Immunity

Several lymphocytes including B cells and T cells express NgR1 (Nogo-A's receptor) and further up-regulate it upon activation of the immune response. R

In the lymph nodes, T cells are activated by dendritic cellls (DCs), which express NgR1 and NgR2 during development, but are downregulated during matruation (which is inversely correlated with myelin). R

Nogo-A And Disease

Nogo-A is up-regulated in:

  • After Stroke R
  • After Spinal Cord Injury R
  • During Epilepsy R
  • During Multiple Sclerosis R
  • During ALS R
  • During Parkinson's Disease R


Benefits Of Inhibiting Nogo-A


1. May Improve Recovery After Tramautic Brain Injury



Nogo-A expression in the brain is significantly increased after stroke. R

Animals treated with anti-Nogo-A antibodies after injury have enhanced neuroplasticity and functional recovery. R R

Although, the ability of hippocampal recovery after stroke using anti-Nogo-A antibodies has been disputed. R

Anyway, inhibiting Nogo-A enhances axonal sprouting and increases dendritic complexity of neurons in the sensorimotor forelimb cortex (this area is important for skilled reaching and motor movements). R

Some studies show that treatment with Nogo-A antibodies after stroke is most effective if it is used by up to one week after injury. R R

It should be noted that inhibiting Nogo-A during stroke worsened the outcome in rodent studies (by increasing apoptosis via p53). R

In contrast, Nogo-A deficient mice that were subjected to traumatic brain injury (TBI) showed significantly worse outcomes than regular mice after TBI. R

2. May Improve Outcome of Spinal Cord Injury

Spinal cord injury (SCI) is associated with axonal disconnection. R

This leads to significant disabilities, even though there can be minimal neuronal death. R

To myelin growth regulators (MAG and OMgp) synergize with Nogo-A to restrict axonal growth after SCI. R

In mice with SCI, a Nogo-A receptor antagonist is able to increase axon regeneration. R

It also increased neuronal reorganization and behavioural improvements. R

In monkeys, Nogo-A antibodies helped improve fine motor movement recovery. R

ATI355, an anti-human Nogo-A antibody, has been shown to be safe for SCI in human clinical trials. R

3. May Improve Parkinson's Disease

Parkinson’s disease (PD) is a neurodegenerative disorder that is mainly characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) with additional loss of dopamine innervation in the striatum. R

Nogo-A expression is high in the SNc in patients with PD. R

One useful strategy to replete the dopaminergic neurons in the brain is with a graft of fetal human ventral mesencepahlic dopaminergic neurons. R

For example, rats with PD were given graft transplants of dopaminergic neurons into their brain and Nogo-A inhibition made this procedure more effective (by two-fold). R

Also, antagonizing Nogo receptors significantly increased dopaminergic cell numbers. R

Tumor necrosis factor alpha (TNFa) and interleukin 6 (IL-6) are two biomarkers for inflammation during PD. R

In a model of PD, Nogo-A inhibition was able to inhibit the increase of TNFa and IL-6 (two proinflammatory cytokines) by lipopolysaccharide (LPS). R

4. Improves Multiple Sclerosis

Nogo-A activation can help identify multiple sclerosis (MS). R

Both Nogo-A and NgR1 are expressed in multiple sclerosis (MS) lesions. R

 In animal models, deactivating Nogo-A expression can help ameliorate MS and promote axonal repair. R R

Using a Nogo-A antibody was able to prevent damage to the spinal cord in MS. R

5. Increases New Memory Formation

In the hippocampus, nogo-a stabilizes the architecture of the hippocampus. R

Nogo-A (along with PirB), also negatively influences long-term potentiation (LTP) in the hippocampus (via modulation of AMPA). R R R

Nogo-A influences spatial learning and memory retention by regulating the use of more efficient hippocampus-dependent strategies. R

So, inhibiting Nogo-A would theoretically allow new memories to form and overwrite old ones. R

This may be helpful for Post-Tramautic Stress Disorder, since Nogo-A expression prevents the erasure of fear memories. R

6. Protects The Eyes During Injury

Nogo-A is highly expressed in Müller glia (a type of retinal glial cell). R

It regulates inflammation and axonal growth of the optic nerve.

For example, overexpression of Nogo-A was able to help promote regeneration of retinal ganglion cells (RGCs) after optic nerve injury. R

In contrast, in multiple studies mice unable to express Nogo-A had significantly better abilities to heal their optic nerve after injury. R R R R R

For example. spatial frequency and contrast sensitivity was increased in Nogo-A deficient mice than regular mice after eye damage. R

Even inhibiting Nogo-A activity had similar results in multiple studies. R R

Also if RGCs were in an active growth state, inhibition of Nogo enhanced optic nerve regeneration even more. R

7. Promotes Angiogenesis

Nogo-A is a negative regulator of angiogensis (the growth of new blood cells). R

In mice, inhibiting Nogo-A increased blood cell formation in the brain. R

In humans, besides Nogo-A, Nogo-B regulates vascular remodeling. R

8. May Increase Healing After Peripheral Nerve Injury

Injured peripheral nerves often regenerate well, but inhibition of Nogo-A promotes their healing, especially of Schwann cells. R

9. May Prevent Hearing Loss

Nogo-A is found in sensory organs such as the inner ear. R

Nogo-A is involved in maintaining a non-regenerative state of hair cells. R

In mice, no hearing loss was observed in 10 month old Nogo-A knock-out mice as compared to wild type. R

10. May Help Amyotrophic Lateral Sclerosis 

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron loss and muscle wasting. R

Nogo can influence the progression of ALS. R

Nogo-A expression is correlated with the severity of symptoms in ALS patients. R R R

Expression may significantly contribute to functional motor impairment. R

A Nogo-A test is able to identify ALS early in the course of the disease when diagnosis is difficult. R

In a human clinical trial, intravenous ozanezumab (anti-Nogo-A antibody) inhibited demylination of the muscle nerve fibers. R

It was also well tolerated shown to be safe. R

There are more human clinical trials showing its efficacy. R

In contrast, in an animal model, inhibiting Nogo-A promoted and worsened ALS. R


Downsides Of Inhibiting Nogo-A


1. May Sprout Irregular Growth

Inhibiting Nogo-A may not only favor sprouting of lesioned axons, but may also induce unspecific growth of axons, causing undesired pathologies. R

Mice that couldn't express Nogo-A had decreased spine density. R

2. May Induce Schizophrenia

in mice that had the Nogo-A gene deleted, they experienced behaviorail abnormalities resembling schizophrenia-related endophenotypes: R

  • deficient sensorimotor gating
  • disrupted latent inhibition
  • perseverative behavior
  • increased sensitivity to the locomotor stimulating effects of amphetamine

They also had altered monoaminergic transmitter levels in specific striatal and limbic structures, as well as changes in dopamine D2 receptor expression in the same brain regions. R

3. May Disrupt Circadian Rhythm

Mice lacking Nogo-A had problems with  motor co-ordination and balance (via modulation of dopaminergic and motor systems). R

This was accompanied with spontaneous locomotor activity. R

Activity was increased in during the night. R

4. May Promote Cancer

Nogo-A acts as a downregulator for tumor growth. R

It is highly expressed in tumors, helping prevent their growth. R

Inhibition can theoretically allow excessive tumor growth, but I would like to see more research on this topic.  

5. May Promote Alzheimer's Disease

Nogo-A/Nogo-A receptors (NgR) modulate the production of amyloid β-protein (Aβ), which is thought to be a major cause of Alzheimer's Disease (AD). R

One way it does this is through mediating neuroinflammation via modulating microglia adhesion and migration. R

The Nogo-A/NgR and the downstream Rho-ROCK pathway inhibits axon outgrowth and synapse remodeling. R

This is an obstacle to neuronal regeneration and blocking the recovery of damaged neural networks in AD. R

PirB is a novel receptor for Nogo-A that interacts with Aβ and mediates its neurotoxicity. R

S1PR2 is also a receptor for Nogo-A that activates ROCK and mediates neuronal plasticity. R

NgR also influences the metabolism of amyloid precursor protein (APP). R

NgR can bind to APP and Aβ. R

In mice, there is an increased Aβ accumulation in the hippocampal dentate gyrus and cerebral cortex of mice lacking NgR. R

Applying NgR(310)ecto-Fc (an Anti-NgR blocking protein) reduced Aβ plaque deposition in those mice. R

Also in cultures, overexpression of NgR decreases Aβ production. R

As mice aging, their ability to bing Nogo-A to Aβ decreases. R

In contrast, blocking reticulon 3 (different than reticulon 4) is beneficial for reducing Aβ. R

Also, in humans Nogo-A is over-expressed in hippocampal neurons in AD and also associated with high levels of Aβ in the hippocampus. R

Nogo is able to bind and inhibit the β-amyloid-converting enzyme 1 (BACE1), which transforms the amyloid precursor protein (APP) into aggregating β-amyloid. R


Mechanism Of Action







Nogo-A (aka reticulon 4) belongs to the reticulon family that consists of four genes named RTN1, RTN2, RTN3 and RTN4. R

RTNs infleunce the curvature of the endoplasmic reticulum (ER) and are structural regulators for the ER. R

RTNs also interact with anti-apoptotic intracellular proteins Bcl-2 or Bcl-XL in regulating cell death. R

RTN4 encodes for three major isoforms (Nogo-A, B and C). R

Nogo-A (Nogo-66 and Nogo-A-D20) naturally binds to its receptor NgR1. R R R

NgR1 has to form a complex with LINGO-1, TROY or p75. R

p75 interacts with GPI and activates the Rho/ROCK pathway. R

Nogo-66 binding with PirB can also activate the Rho/ROCK pathway. R

Neurite growth inhibition is regulated by RhoB, Rac1, and TSPAN3 (tetraspanin-3). R R R

Nogo-A turns on RhoA, but deactivates RhoB and Rac1. R

When Nogo-A binds to Sphingolipid Receptor S1PR2, synaptic plasticity is surpressed. R

Nogo-D20 works via S1PR2. R



  • Activates RhoA R
  • Antagonizes mTOR (for LTP) R
  • Downregulates cAMP R
  • Lowers ROS R

Nogo-A Inhibition:

  • Decreases IGF-1 (in hippocampus) R
  • Does not affect CGRP R
  • Increases BDNF R
  • Increases Dopaminergic neurons R
  • Increases FGF2 R
  • Increases GAP43 R
  • Increases Glutamate AMPA and NMDA receptors (in hippocampus) R
  • Increases NGF R
  • Increases VEGF R
  • Inhibits IL-6 R
  • Inhibits TNFalpha R


How To Inhibit Nogo-A




  • Anti-Nogo-A Antibodies (to such as LINGO-1, ROCK, and ATI355) R R R R
  • Fasudil R
  • Ganglioside (GM1 activation) R
  • GPR50 Expression R
  • LILRA3 R
  • Nogo-66 antagonist peptides R
  • Ozanezumab R
  • TAT-M9 and TAT-NEP1-40 (but also increases expression of Tau GAP43 and MAP-2)


More Research


  • Rewiring induced by the Nogo-A–specific antibody treatment did not generate chronic pain. R
  • Nogo-A does not inhibit retinal axon regeneration in the lizard Gallotia galloti. R
  • Easier deilvery of anti-nogo peptides can be made in alginate nanospheres. R
  • More on Nogo-A signaling pathways R


It may look weird since i just copied and pasted all from the page https://www.livinghe...city-switch-ltp

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#3 Pereise1

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Posted 19 April 2017 - 10:16 PM



Thanks for all that amazing information! This will definitely be a huge help.

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#4 monowav

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Posted 20 April 2017 - 06:56 PM




Thanks for all that amazing information! This will definitely be a huge help.



Also tagged with one or more of these keywords: neurogenesis, bdnf, neurod1, nogo, stroke, narcolepsy

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