Preview

Neurology, Neuropsychiatry, Psychosomatics

Advanced search

Chondroprotectors as modulators of neuroinflammation

https://doi.org/10.14412/2074-2711-2023-1-110-118

Abstract

Modern fundamental and clinical studies show that chondroprotector molecules (chondroitin sulfate – CS; glucosamine sulfate – GS) can be useful in the treatment of neuroinflammation and so-called "inflammageing" – chronic, low-grade systemic inflammation that stimulates the development of neurodegeneration, atherosclerosis, ischemia, osteoarthritis and other pathologies. The role of CS and GS in the central nervous system are evident in the context of the concepts of the tetrapartite synapse and perineuronal nets (PNNs). Molecular mechanisms of action of CS and GS on neuroinflammation include: 1) interaction with the CD44 receptor, leading to inhibition of the pro-inflammatory factor NFκB, antiatherosclerotic and anticoagulant effects; 2) direct contribution to the formation of the PNNs, which support the division and differentiation of neurons; 3) inhibition of Toll-like receptors; 4) antioxidant and neuroprotective properties through activation of the PKC/PI3K/Akt signaling pathway; 5) inhibition of matrix metalloproteinases. These molecular effects determine the neuroprotective properties of CS/GS in ischemia, neurodegeneration, and pain syndromes associated with neuroinflammation.

About the Authors

I. Y. Torshin
Institute of Pharmacoinformatics of the Federal Research Center “Computer Science and Management”, Russian Academy of Sciences
Russian Federation

119333, Moscow, Vavilov St., 44, Build. 2


Competing Interests:

The article expresses the position of the authors, which may differ from that of Sotex PharmFirma.



O. A. Gromova
Institute of Pharmacoinformatics of the Federal Research Center “Computer Science and Management”, Russian Academy of Sciences
Russian Federation

Olga Alekseevna Gromova

119333, Moscow, Vavilov St., 44, Build. 2


Competing Interests:

The article expresses the position of the authors, which may differ from that of Sotex PharmFirma.



A. G. Nazarenko
N.N. Priorov National Medical Research Center of Traumatology and Orthopedics
Russian Federation

127299, Moscow, Priorova St., 10


Competing Interests:

The article expresses the position of the authors, which may differ from that of Sotex PharmFirma.



References

1. Sarvilina IV, Lila AM, Gromova OA, Torshin IYu. Analysis of the mechanisms of development of neurorheumatological consequences of COVID-19 and the possibility of their pharmacological correction. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2022;16(2):92-8. doi:10.14412/1996-7012-2022-2-92-98 (In Russ.).

2. Torshin IYu, Gromova OA, Lila AM, et al. The results of postgenomic analysis of a glucosamine sulfate molecule indicate theprospects of treatment for comorbidities. Sovremennaya revmatologiya = Modern Rheumatology Journal. 2018;12(4):129-36. doi:10.14412/1996-7012-2018-4-129-136 (In Russ.).

3. Gromova OA, Torshin IYu, Semenov VA, et al. On the neurological roles of chondroitin sulfate and glucosamine sulfate: a systematic analysis. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2019;11(3):137-43. doi:10.14412/2074-2711-2019-3-137-143 (In Russ.).

4. Chelini G, Pantazopoulos H, Durning P, Berretta S. The tetrapartite synapse: a key concept in the pathophysiology of schizophrenia. Eur Psychiatry. 2018 Apr;50:60-9. doi:10.1016/j.eurpsy.2018.02.003. Epub 2018 Mar 2.

5. Canning DR, Brelsford NR, Lovett NW. Chondroitin sulfate effects on neural stem cell differentiation. In Vitro Cell Dev Biol Anim. 2016 Jan;52(1):35-44. doi:10.1007/s11626-015-9941-8

6. Dyck SM, Karimi-Abdolrezaee S. Chondroitin sulfate proteoglycans: Key modulators in the developing and pathologic central nervous system. Exp Neurol. 2015 Jul;269:169-87. doi:10.1016/j.expneurol.2015.04.006

7. Belova OV, Aref'eva TI, Moskvina SN. Immunological aspects of Parkinson's disease. Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2020;120(2):110-9. doi:10.17116/jnevro2020120021110 (In Russ.).

8. Ghorbani S, Yong VW. The extracellular matrix as modifier of neuroinflammation and remyelination in multiple sclerosis. Brain. 2021 Aug 17;144(7):1958-73. doi:10.1093/brain/awab059

9. Jang DG, Sim HJ, Song EK, et al. Extracellular matrixes and neuroinflammation. BMB Rep. 2020 Nov;53(10):491-9. doi:10.5483/BMBRep.2020.53.10.156

10. Bosiacki M, Gassowska-Dobrowolska M, Kojder K, et al. Perineuronal Nets and Their Role in Synaptic Homeostasis. Int J Mol Sci. 2019 Aug 22;20(17):4108. doi:10.3390/ijms20174108

11. Canas N, Gorina R, Planas AM, et al. Chondroitin sulfate inhibits lipopolysaccharideinduced inflammation in rat astrocytes by preventing nuclear factor kappa B activation. Neuroscience. 2010 May 19;167(3):872-9. doi:10.1016/j.neuroscience.2010.02.069

12. Lila AM, Torshin IYu, Gromova OA. Is it worthwhile rethinking the positive experience of the last 50 years of using chondroitin sulfates against atherosclerosis? FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2020;13(2):184-91. doi:10.17749/2070-4909/farmakoekonomika.2020.043 (In Russ.).

13. Torshin IYu, Lila AM, Gromova OA, et al. Anticoagulant and antiplatelet effects of chondroitin sulfate. RMJ. 2020;(7):44-8 (In Russ.).

14. Yamada J, Maeda S, Soya M, et al. Alleviation of cognitive deficits via upregulation of chondroitin sulfate biosynthesis by lignan sesamin in a mouse model of neuroinflammation. J Nutr Biochem. 2022 Oct;108:109093. doi:10.1016/j.jnutbio.2022.109093

15. McCrary MR, Jiang MQ, Jesson K, et al. Glycosaminoglycan scaffolding and neural progenitor cell transplantation promotes regenerative immunomodulation in the mouse ischemic brain. Exp Neurol. 2022 Nov;357:114177. doi:10.1016/j.expneurol.2022.114177. Epub 2022 Jul 20.

16. Yao M, Fang J, Li J, et al. Modulation of the proteoglycan receptor PTPσ promotes white matter integrity and functional recovery after intracerebral hemorrhage stroke in mice. J Neuroinflammation. 2022 Aug 18;19(1):207. doi:10.1186/s12974-022-02561-4

17. Karumbaiah L, Enam SF, Brown AC, et al. Chondroitin Sulfate Glycosaminoglycan Hydrogels Create Endogenous Niches for Neural Stem Cells. Bioconjug Chem. 2015 Dec 16;26(12):2336-49. doi:10.1021/acs.bioconjchem.5b00397

18. Rauvala H, Paveliev M, Kuja-Panula J, Kulesskaya N. Inhibition and enhancement of neural regeneration by chondroitin sulfate proteoglycans. Neural Regen Res. 2017 May;12(5):687-91. doi:10.4103/1673-5374.206630

19. Wu Y, Sheng W, Chen L, et al. Versican V1 isoform induces neuronal differentiation and promotes neurite outgrowth. Mol Biol Cell. 2004 May;15(5):2093-104. doi:10.1091/mbc.e03-09-0667

20. Liu C, Fan L, Xing J, et al. Inhibition of astrocytic differentiation of transplanted neural stem cells by chondroitin sulfate methacrylate hydrogels for the repair of injured spinal cord. Biomater Sci. 2019 Apr 23;7(5):1995-2008. doi:10.1039/c8bm01363b

21. Betancur MI, Mason HD, Alvarado-Velez M, et al. Chondroitin Sulfate Glycosaminoglycan Matrices Promote Neural Stem Cell Maintenance and Neuroprotection Post-Traumatic Brain Injury. ACS Biomater Sci Eng. 2017 Mar 13;3(3):420-30. doi:10.1021/acsbiomaterials.6b00805

22. Torshin IYu, Gromova OA, Lila AM, et al. Toll-like receptors as a part of osteoarthritis pathophysiology: anti-inflammatory, analgesic and neuroprotective effects. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2021;13(4):123-9. doi:10.14412/2074-2711-2021-4-123-129 (In Russ.).

23. Zhao N, Wu L, Zhang X, et al. Low molecular weight chondroitin sulfate ameliorates pathological changes in 5XFAD mice by improving various functions in the brain. Neuropharmacology. 2021 Nov 1;199:108796. doi:10.1016/j.neuropharm.2021.108796

24. Alfonso-Loeches S, Pascual M, Gomez-Pinedo U, et al. Toll-like receptor 4 participates in the myelin disruptions associated with chronic alcohol abuse. Glia. 2012 May;60(6):948-64. doi:10.1002/glia.22327

25. Calamia V, Lourido L, Fernandez-Puente P, et al. Secretome analysis of chondroitin sulfatetreated chondrocytes reveals anti-angiogenic, anti-inflammatory and anti-catabolic properties. Arthritis Res Ther. 2012 Oct 2;14(5):R202. doi:10.1186/ar4040

26. Cauwe B, van den Steen PE, Opdenakker G. The biochemical, biological, and pathological kaleidoscope of cell surface substrates processed by matrix metalloproteinases. Crit Rev Biochem Mol Biol. 2007 MayJun;42(3):113-85. doi:10.1080/10409230701340019

27. Shingleton WD, Hodges DJ, Brick P, Cawston TE. Collagenase: a key enzyme in collagen turnover. Biochem Cell Biol. 1996;74(6):759-75. doi:10.1139/o96-083

28. Lila AM, Gromova OA, Torshin IYu, et al. Molecular effects of chondroguard in osteoarthritis and herniated discs. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2017;9(3):88-97. doi:10.14412/2074-2711-2017-3-88-97 (In Russ.).

29. Martin-de-Saavedra MD, del Barrio L, Canas N, et al. Chondroitin sulfate reduces cell death of rat hippocampal slices subjected to oxygen and glucose deprivation by inhibiting p38, NFkappaB and iNOS. Neurochem Int. 2011 May;58(6):676-83. doi:10.1016/j.neuint.2011.02.006

30. Egea J, Garcia AG, Verges J, et al. Antioxidant, antiinflammatory and neuroprotective actions of chondroitin sulfate and proteoglycans. Osteoarthritis Cartilage. 2010 Jun;18 Suppl 1:S24-7. doi:10.1016/j.joca.2010.01.016

31. Chen R, Gong P, Tao T, et al. O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity. Cell Mol Neurobiol. 2017 Nov;37(8):1465-75. doi:10.1007/s10571-017-0477-1

32. Fluri F, Grunstein D, Cam E, et al. Fullerenols and glucosamine fullerenes reduce infarct volume and cerebral inflammation after ischemic stroke in normotensive and hypertensive rats. Exp Neurol. 2015 Mar;265:142-51. doi:10.1016/j.expneurol.2015.01.005

33. Hwang SY, Shin JH, Hwang JS, et al. Glucosamine exerts a neuroprotective effect via suppression of inflammation in rat brain ischemia/reperfusion injury. Glia. 2010 Nov 15;58(15):1881-92. doi:10.1002/glia.21058

34. Jhelum P, Radhakrishnan M, Paul ARS, et al. Neuroprotective and Proneurogenic Effects of Glucosamine in an Internal Carotid Artery Occlusion Model of Ischemia. Neuromolecular Med. 2022 Sep;24(3):268-73. doi:10.1007/s12017-021-08697-5

35. Zhang Q, Li J, Liu C, et al. Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Abeta)-induced damage in vitro and in vivo. Neuroscience. 2015 Oct 1;305:169-82. doi:10.1016/j.neuroscience.2015.08.002

36. Wang G, Zhou HH, Luo L, et al. Voluntary wheel running is capable of improving cognitive function only in the young but not the middleaged male APPSwe/PS1De9 mice. Neurochem Int. 2021 May;145:105010. doi:10.1016/j.neuint.2021.105010

37. Nemoto W, Yamada K, Nakagawasai O, et al. Effect of repeated oral administration of chondroitin sulfate on neuropathic pain induced by partial sciatic nerve ligation in mice. J Pharmacol Sci. 2018 Aug;137(4):403-6. doi:10.1016/j.jphs.2018.03.003. Epub 2018 Mar 23.

38. Nemoto W, Yamada K, Ogata Y, et al. Chondroitin sulfate attenuates formalininduced persistent tactile allodynia. J Pharmacol Sci. 2016 Aug;131(4):275-8. doi:10.1016/j.jphs.2016.07.009

39. Samartcev IN, Zhivolupov SA, Barantsevich ER, Danilov AB. The evaluation of the efficacy of Alflutop in the complex treatment of patients with chronic lower back pain (the observational study ZEITNOT). Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2021;121(2):24-30. doi:10.17116/jnevro202112102124 (In Russ.).


Review

For citations:


Torshin IY, Gromova OA, Nazarenko AG. Chondroprotectors as modulators of neuroinflammation. Nevrologiya, neiropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics. 2023;15(1):110-118. (In Russ.) https://doi.org/10.14412/2074-2711-2023-1-110-118

Views: 611


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)