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 Falcón-Cama

doi: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.

Highlights

Myelin is a lipid-rich structure that wraps the axons in a multilayered organization, as cellular membrane extensions of oligodendrocytes (ODs) or Schwann cells in the central or peripheral nervous systems, respectively
It is imperative to design novel therapeutic strategies aimed at promoting remyelination in the central nervous system (CNS), preferably at the early stages following the onset of Multiple Sclerosis (MS), which may stop the decline toward the progressive phase of the disease
We discussed previous studies from our group showing that C-PC, given in therapeutic regimens, promoted white matter regeneration in the CNS of rats and mice affected by EAE

Summary

Introduction

Myelin is a lipid-rich structure that wraps the axons in a multilayered organization, as cellular membrane extensions of oligodendrocytes (ODs) or Schwann cells in the central or peripheral nervous systems, respectively. Around 80% of those patients that do not receive any disease-modifying treatment evolve into the secondary progressive phase of the illness (SPMS) within 20 years after the onset [10] In this subset of patients, the inflammatory-demyelinating injury is disseminated and they experience an insidious worsening of clinical symptoms and the accumulation of neurologic disability unrelated to any acute attacks. It is imperative to design novel therapeutic strategies aimed at promoting remyelination in the CNS, preferably at the early stages following the onset of MS, which may stop the decline toward the progressive phase of the disease During this progressive phase of MS, acute inflammatory relapses are scarce but there is increasing loss of neuronal function and extensive demyelination and the stimulation of endogenous remyelination would potentially have the greatest clinical impact [19]. Discuss and comment results from our group and other authors demonstrating the beneficial actions of these compounds in experimental models of MS and IS as remyelination inducing agents, which support their medical application for these diseases

C-Phycocyanin and Phycocyanobilin

Mechanisms of Remyelination

C-PC Remyelinating Actions in MS Models

Findings

Conclusions