C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective

Giselle Pentón-Rol; Javier Marín-Prida; Viviana Falcon-Cama

doi:10.3390/bs8010015

journal article Open Access Jan 18, 2018

C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective

Giselle Pentón-Rol Javier Marín-Prida Viviana Falcon-Cama

Behavioral Sciences Vol. 8 No. 1 pp. 15 · MDPI AG

View at Publisher Save 10.3390/bs8010015

Abstract

Myelin loss has a crucial impact on behavior disabilities associated to Multiple Sclerosis (MS) and Ischemic Stroke (IS). Although several MS therapies are approved, none of them promote remyelination in patients, limiting their ability for chronic recovery. With no available therapeutic options, enhanced demyelination in stroke survivors is correlated with a poorer behavioral recovery. Here, we show the experimental findings of our group and others supporting the remyelinating effects of C-Phycocyanin (C-PC), the main biliprotein of Spirulina platensis and its linked tetrapyrrole Phycocyanobilin (PCB), in models of these illnesses. C-PC promoted white matter regeneration in rats and mice affected by experimental autoimmune encephalomyelitis. Electron microscopy analysis in cerebral cortex from ischemic rats revealed a potent remyelinating action of PCB treatment after stroke. Among others biological processes, we discussed the role of regulatory T cell induction, the control of oxidative stress and pro-inflammatory mediators, gene expression modulation and COX-2 inhibition as potential mechanisms involved in the C-PC and PCB effects on the recruitment, differentiation and maturation of oligodendrocyte precursor cells in demyelinated lesions. The assembled evidence supports the implementation of clinical trials to demonstrate the recovery effects of C-PC and PCB in these diseases.

Topics

No keywords indexed for this article. Browse by subject →

References

108

[1]

Philips "Oligodendroglia: Metabolic supporters of neurons" J. Clin. Investig. (2017) 10.1172/jci90610

[2]

Snaidero "Myelination at a glance" J. Cell Sci. (2014) 10.1242/jcs.151043

[3]

Kremer "Pushing forward: Remyelination as the new frontier in CNS diseases" Trends Neurosci. (2016) 10.1016/j.tins.2016.02.004

[4]

Motor compensation and its effects on neural reorganization after stroke

Theresa A. Jones

Nature Reviews Neuroscience 2017 10.1038/nrn.2017.26

[5]

Mark "Stroke and Behavior" Neurol. Clin. (2016) 10.1016/j.ncl.2015.08.009

[6]

Zhou, J., Zhuang, J., Li, J., Ooi, E., Bloom, J., Poon, C., Lax, D., Rosenbaum, D.M., and Barone, F.C. (2013). Long-term post-stroke changes include myelin loss, specific deficits in sensory and motor behaviors and complex cognitive impairment detected using active place avoidance. PLoS ONE, 8. 10.1371/journal.pone.0057503

[7]

Ho "Is white matter involved in patients entered into typical trials of neuroprotection?" Stroke (2005) 10.1161/01.str.0000189748.52500.a7

[8]

Wang "Degeneration of corpus callosum and recovery of motor function after stroke: A multimodal magnetic resonance imaging study" Hum. Brain Mapp. (2012) 10.1002/hbm.21417

[9]

Nylander "Multiple sclerosis" J. Clin. Investig. (2012) 10.1172/jci58649

[10]

Whitwell "Setting new standards in multiple sclerosis care and research" Lancet Neurol. (2012) 10.1016/s1474-4422(12)70214-4

[11]

Gelfand "Multiple sclerosis: Diagnosis, differential diagnosis and clinical presentation" Handb. Clin. Neurol. (2014) 10.1016/b978-0-444-52001-2.00011-x

[12]

Ziemssen "Symptom management in patients with multiple sclerosis" J. Neurol. Sci. (2011) 10.1016/s0022-510x(11)70009-0

[13]

Simmons "Living with multiple sclerosis: Longitudinal changes in employment and the importance of symptom management" J. Neurol. (2010) 10.1007/s00415-009-5441-7

[14]

Westad "The multiple sclerosis market" Nat. Rev. Drug Discov. (2017) 10.1038/nrd.2017.107

[15]

Montalban "Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis" N. Engl. J. Med. (2017) 10.1056/nejmoa1606468

[16]

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Stephen L. Hauser, Amit Bar-Or, Giancarlo Comi et al.

New England Journal of Medicine 2017 10.1056/nejmoa1601277

[17]

FDA News Release (2017, November 08). FDA Approves New Drug to Treat Multiple Sclerosis. First Drug Approved for Primary Progressive MS, Available online: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm549325.htm.

[18]

Dendrou "Immunomodulation in multiple sclerosis: Promises and pitfalls" Curr. Opin. Immunol. (2017) 10.1016/j.coi.2017.08.013

[19]

Kremer "Promoting remyelination in multiple sclerosis: Current drugs and future prospects" Mult. Scler. (2015) 10.1177/1352458514566419

[20]

Romay "Antioxidant and anti-inflammatory properties of C-phycocyanin from blue-green algae" Inflamm. Res. (1998) 10.1007/s000110050256

[21]

Clinical Potential of Spirulina as a Source of Phycocyanobilin

Mark F. McCarty

Journal of Medicinal Food 2007 10.1089/jmf.2007.621

[22]

Fu "Mass-spectral identification and purification of phycoerythrobilin and phycocyanobilin" Biochem. J. (1979) 10.1042/bj1790001

[23]

Mukougawa "Metabolic engineering to produce phytochromes with phytochromobilin, phycocyanobilin, or phycoerythrobilin chromophore in Escherichia coli" FEBS Lett. (2006) 10.1016/j.febslet.2006.01.051

[24]

"Nutraceutical properties of phycocyanin" J. Funct. Food (2014) 10.1016/j.jff.2014.10.011

[25]

Remirez "Role of histamine in the inhibitory effects of phycocyanin in experimental models of allergic inflammatory response" Mediat. Inflamm. (2002) 10.1080/09629350220131926

[26]

Leung, P.O., Lee, H.H., Kung, Y.C., Tsai, M.F., and Chou, T.C. (2013). Therapeutic effect of C-phycocyanin extracted from blue green algae in a rat model of acute lung injury induced by lipopolysaccharide. Evid. Based Complement. Altern. Med., 916590. 10.1155/2013/916590

[27]

Franklin "Why does remyelination fail in multiple sclerosis?" Nat. Rev. Neurosci. (2002) 10.1038/nrn917

[28]

Kuhlmann "Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis" Brain (2008) 10.1093/brain/awn096

[29]

Remyelination in the CNS: from biology to therapy

Robin J. M. Franklin, Charles ffrench-Constant

Nature Reviews Neuroscience 2008 10.1038/nrn2480

[30]

McMurran "CNS remyelination and the innate immune system" Front. Cell Dev. Biol. (2016) 10.3389/fcell.2016.00038

[31]

Zawadzka "CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination" Cell Stem Cell (2010) 10.1016/j.stem.2010.04.002

[32]

Irvine "Remyelination protects axons from demyelination-associated axon degeneration" Brain (2008) 10.1093/brain/awn080

[33]

Kreutzfeldt "Late motor decline after accomplished remyelination: Impact for progressive multiple sclerosis" Ann. Neurol. (2012) 10.1002/ana.22681

[34]

Boulanger "From precursors to myelinating oligodendrocytes: Contribution of intrinsic and extrinsic factors to white matter plasticity in the adult brain" Neuroscience (2014) 10.1016/j.neuroscience.2014.03.063

[35]

Chang "Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis" N. Engl. J. Med. (2002) 10.1056/nejmoa010994

[36]

Chamberlain "Oligodendrocyte regeneration: Its significance in myelin replacement and neuroprotection in multiple sclerosis" Neuropharmacology (2016) 10.1016/j.neuropharm.2015.10.010

[37]

Arai "An oligovascular niche: Cerebral endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells" J. Neurosci. (2009) 10.1523/jneurosci.0035-09.2009

[38]

Domingues "Oligodendrocyte, astrocyte and microglia crosstalk in myelin development, damage and repair" Front. Cell Dev. Biol. (2016)

[39]

Plemel "Remyelination therapies: A new direction and challenge in multiple sclerosis" Nat. Rev. Drug Discov. (2017) 10.1038/nrd.2017.115

[40]

Itoh "Mechanisms of cell-cell interaction in oligodendrogenesis and remyelination after stroke" Brain Res. (2015) 10.1016/j.brainres.2015.04.039

[41]

Denic "The relevance of animal models in multiple sclerosis research" Pathophysiology (2011) 10.1016/j.pathophys.2010.04.004

[42]

C-Phycocyanin ameliorates experimental autoimmune encephalomyelitis and induces regulatory T cells

Giselle Pentón-Rol, Gregorio Martínez-Sánchez, Majel Cervantes-Llanos et al.

International Immunopharmacology 2011 10.1016/j.intimp.2010.10.001

[43]

Olsen "Remyelination in multiple sclerosis: Cellular mechanisms and novel therapeutic approaches" J. Neurosci. Res. (2015) 10.1002/jnr.23493

[44]

Haider "The topography of demyelination and neurodegeneration in the multiple sclerosis brain" Brain (2016) 10.1093/brain/awv398

[45]

Wrzos "Differential contribution of immune effector mechanisms to cortical demyelination in multiple sclerosis" Acta Neuropathol. (2017) 10.1007/s00401-017-1706-x

[46]

Santis "Structure of the gene coding for the human early lymphocyte activation antigen CD69: A C-type lectin receptor evolutionarily related with the gene families of natural killer cell-specific receptors" Eur. J. Immunol. (1994) 10.1002/eji.1830240735

[47]

Koutrolos "Treg cells mediate recovery from EAE by controlling effector T cell proliferation and motility in the CNS" Acta Neuropathol. Commun. (2014) 10.1186/s40478-014-0163-1

[48]

Saresella "CD4+CD25+FoxP3+PD1− regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy" FASEB J. (2008) 10.1096/fj.08-110650

[49]

Dombrowski "Regulatory T cells promote myelin regeneration in the central nervous system" Nat. Neurosci. (2017) 10.1038/nn.4528

[50]

Simmons "Cyclooxygenase isozymes: The biology of prostaglandin synthesis and inhibition" Pharmacol. Rev. (2004) 10.1124/pr.56.3.3

Showing 50 of 108 references

Cited By

40

C-Phycocyanin: A Phycobiliprotein from Spirulina with Metabolic Syndrome and Oxidative Stress Effects

Van D. Castro-Gerónimo, Rosa Virginia García-Rodríguez · 2024

Journal of Medicinal Food

Probing the potential of mercury removal by covalently immobilized phycobiliproteins onto the surface of chitosan beads

Jelena Radović, Dragana Popović · 2024

Algal Research

Phycocyanin from Spirulina: A comprehensive review on cultivation, extraction, purification, and its application in food and allied industries

Kerthika Devi Athiyappan, Winny Routray · 2024

Food and Humanity

The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome

Javier Marín-Prida, Arielis Rodríguez-Ulloa · 2023

Frontiers in Immunology

Anti-inflammatory mechanisms and pharmacological actions of phycocyanobilin in a mouse model of experimental autoimmune encephalomyelitis: A therapeutic promise for multiple sclerosis

Javier Marín-Prida, Nancy Pavón-Fuentes · 2022

Frontiers in Immunology

Nutraceutical and therapeutic potential of Phycocyanobilin for treating Alzheimer’s disease

Beatriz Piniella-Matamoros, Javier Marín-Prida · 2021

Journal of Biosciences

Metrics

40

Citations

108

References

Details

Published: Jan 18, 2018
Vol/Issue: 8(1)
Pages: 15
License: View

Authors

G

Giselle Pentón-Rol

Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Cubanacan, P.O. Box 6162, Playa, Havana 10600, Cuba

J

Javier Marín-Prida

Center for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/214 y 222, La Lisa, PO Box 430, Havana 13600, Cuba

V

Viviana Falcon-Cama

Center for Genetic Engineering and Biotechnology (CIGB), Ave. 31 e/158 y 190, Cubanacan, P.O. Box 6162, Playa, Havana 10600, Cuba

Cite This Article

Giselle Pentón-Rol, Javier Marín-Prida, Viviana Falcon-Cama (2018). C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective. Behavioral Sciences, 8(1), 15. https://doi.org/10.3390/bs8010015

C-Phycocyanin and Phycocyanobilin as Remyelination Therapies for Enhancing Recovery in Multiple Sclerosis and Ischemic Stroke: A Preclinical Perspective

You May Also Like