Inosine

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Information on nutritional supplements people with ALS have been taking

Wikipedia page

Inosine has been thought of in the B vitamin family, although it is not technically a vitamin because your body can synthesize it. It is a basic component of cells and participates in the synthesis of energy. Inosine is naturally formed as a result of purine metabolism. Purines fix nitrogen for use as basic building blocks of RNA and DNA. As inosine is formed it goes on to participate in the synthesis of ATP (cellular energy). Since inosine is readily formed as a byproduct of purine metabolism, we do not typically think of it as a needed dietary supplement. [ health news ]


Effects on ALS

Inosine acts as a competitor of 6-TG, suggesting that it acts as an N-kinase agonist, and that this kinase is part of a modular signal transduction pathway controlling axon growth. Following unilateral transections of the corticospinal tract in mature rats, inosine applied to the intact sensorimotor cortex stimulated layer 5 pyramidal cells to upregulate GAP-43 expression and to sprout axon collaterals that crossed the midline and reinnervated regions of the cervical spinal cord which had lost their normal afferents. [2]

Discussion threads on the ALSTDI forum

Regulator found for regenerating nerve fibers in animals:

A possible combined cocktail for nerve regeneration?
inosine - target

1. Mst3b 2. GAP-43 3. Talpha-1 tubulin

ibuprofen - target RhoA inhibition
Vitamin D - target CD1c⁺ mDCs/RALDH2 mRNA


Regulated pathways

Upregulates GAP-43

Probable N-kinase agonist

References

[1] <bibtex> @article{Benowitz1999, abstract = {The purine nucleoside inosine has been shown to induce axon outgrowth from primary neurons in culture through a direct intracellular mechanism. For this study, we investigated the effects of inosine in vivo by examining whether it would stimulate axon growth after a unilateral transection of the corticospinal tract. Inosine applied with a minipump to the rat sensorimotor cortex stimulated intact pyramidal cells to undergo extensive sprouting of their axons into the denervated spinal cord white matter and adjacent neuropil. Axon growth was visualized by anterograde tracing with biotinylated dextran amine and by immunohistochemistry with antibodies to GAP-43. Thus, inosine, a naturally occurring metabolite without known side effects, might help to restore essential circuitry after injury to the central nervous system.}, author = {Benowitz, L I and Goldberg, D E and Madsen, J R and Soni, D and Irwin, N}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {Animals,Axons,Axons: drug effects,Inosine,Inosine: pharmacology,Male,Pyramidal Tracts,Pyramidal Tracts: drug effects,Pyramidal Tracts: injuries,Rats,Rats, Sprague-Dawley}, mendeley-groups = {inosine}, month = nov, number = {23}, pages = {13486--90}, pmid = {10557347}, title = Template:Inosine stimulates extensive axon collateral growth in the rat corticospinal tract after injury., url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=23974\&tool=pmcentrez\&rendertype=abstract}, volume = {96}, year = {1999} } </bibtex>

[2] <bibtex> @article{Benowitz2001, abstract = {Axon growth is characterized by a distinctive program of gene expression. We present evidence here that this program is regulated through a purine-sensitive mechanism, and that it can be re-activated in mature CNS neurons to induce extensive axon growth in vitro and in vivo. In dissociated goldfish retinal ganglion cells, the purine nucleoside inosine acts intracellularly to stimulate axon outgrowth by inducing the expression of GAP-43, Talpha-1 tubulin, and other growth-associated proteins. The purine analog 6-thioguanine (6-TG) acts in the opposite fashion, blocking axon growth and the underlying program of molecular changes. Prior studies in PC12 cells have shown that 6-TG selectively inhibits the activity of N-kinase, a 47-49 kDa serine-threonine kinase. Inosine acts as a competitor of 6-TG, suggesting that it acts as an N-kinase agonist, and that this kinase is part of a modular signal transduction pathway controlling axon growth. Following unilateral transections of the corticospinal tract in mature rats, inosine applied to the intact sensorimotor cortex stimulated layer 5 pyramidal cells to upregulate GAP-43 expression and to sprout axon collaterals that crossed the midline and reinnervated regions of the cervical spinal cord which had lost their normal afferents. It will now be important to identify the molecular changes that lie upstream and downstream of N-kinase, and to explore the clinical potential of activating this pathway in patients who have sustained CNS injury.}, author = {Benowitz, L I and Goldberg, D E and Irwin, N}, issn = {0922-6028}, journal = {Restorative neurology and neuroscience}, keywords = {Animals,Axons,Axons: physiology,Cell Division,Cell Division: physiology,Humans,Inosine,Inosine: chemistry,Inosine: physiology,Purines,Purines: chemistry,Purines: pharmacology,Retinal Ganglion Cells,Retinal Ganglion Cells: cytology,Retinal Ganglion Cells: physiology,Spinal Cord,Spinal Cord: cytology,Spinal Cord: physiology}, mendeley-groups = {inosine}, month = jan, number = {1-2}, pages = {41--9}, pmid = {12082228}, title = Template:A purine-sensitive mechanism regulates the molecular program for axon growth., url = {http://www.ncbi.nlm.nih.gov/pubmed/12082228}, volume = {19}, year = {2001} } </bibtex>