Peptides for EAE induction

Multiple Sclerosis 

Multiple sclerosis (MS) is a degenerative disorder that affects the central nervous system (CNS), specifically the brain and the spinal cord. This disease is also known as encephalomyelitis disseminate. Damages dealed to the myelin sheath covers of nerve cells in the brain and the spinal cord are due to the demyelinating disease (destruction of myelin, the fatty tissue that surrounds and protects the nerve fibers and promotes the transmission of nerve impulses).

Fig. 1 – Comparison between a healthy axone with its myelin and one affected by multiple sclerosis

Myelin composition

Myelin sheath is a discontinue membrane-like structure that surrounds nerve cell axons to insulate them and increase the rate of action potentials. Short gaps between the myelinated section is called nodes of Ranvier.
The CNS myelin is composed about 40% of water and 60% of dry mass in aim of the insulation of the nerves. Dry mass contains around 75% of lipid and 20% of protein. Protein percentage includes 3 different proteins : firstly, myelin oligodendrocyte glycoprotein (MOG), which is specific to the CNS, secondly proteolipid protein (PLP), which is the most abundant protein in CNS myelin and finally myelin basic protein (MBP) that plays a role in organization of the structure of myelin sheaths.
Some of parts of this protein (peptide) are the most exposed to the environment.
When EAE is triggered, this exposed part become an epitope focus of the immune system. So the proteins are damaged and they can’t manage their role of insulation. Find here the different structure of these myelin structural protein.

Myelin Oligdendrocyte Glycoprotein

Fig. 2 – MOG Structure

MOG (Myelin Oligodendrocyte Glycoprotein – UniProtKB – H0Y8A0) is a structural protein expressed in the outer surface of the myelin sheath, that surronds neurons and axon to provide efficient action potential electrical conduction. Injection of a fragment of this protein (peptide) leads to the EAE.

Myelin Basic Protein

Fig. 3 – MBP Structure

MBP (Myelin Basic Protein –  UniProtKB – P02686) is a structural protein found in the inner myelin layer and plays a role in the organization ot the structure. Studies about the pathogenesis of the autimmune neurodegenerative disease multiple sclerosis MBP has been identified as a factor.

Proteolipid Protein

Fig. 4 – PLP Structure

PLP (ProteoLipid Protein UniProtKB – B1B1G1) is the major myelin protein from the central nervous system. It plays a crucial role in the maintenance and creation of the structure of the myelin. Induction of a T cell mediated chronic relapsing autoimmune encephalomyelitis in animals and therefore is a candidate for an antigen involved in the pathogenesis of multiple sclerosis.

Immunology of Multiple sclerosis

Actually, it is known that the development of the Multiple sclerosis is due to a predisposing genetic trait and requires an inciting environmental insult such as a viral infection (1). Target tissues’s damages are due mostly to autoreactive CD8+ T cells, antibodies against myelin (i.e. anti-PLP, anti-MOG, anti-MBP) and factors produce by innate immune cells (i.e. IFN, cytokines…). CD4+ T cells and their differentiation into Th1 phenotype are important in the initial steps of the disease and during the evolution of the multiple sclerosis.

Treatments for multiple sclerosis

No cure are known for Multiple sclerosis at the moment. Drugs used to help against MS in general prevent new attacks or attempt to improve the function after attack, but they have side effects. However some therapies exist like, firstly plasmapheresis (remove and exchange the blood plasma to take off antibodies), secondly kinesitherapy (treatment of disease by passive and active muscular movement), in addition of the occupational therapy (re-education, readaptation or even rehabilitation, through the activity) and finally immunotherapies (treatment by activating or suppressing the immune system).

In order to develop new treatments, researchers use various models. A frequently used model consists in inducing a MS phenotype in mice to study the demyelination of the CNS. This technique consists in injecting an antigen peptide in mice to create an experimental model nammed EAE or Experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE)

Experimental autoimmune encephalomyelitis (EAE) is one of the most popular animal models of multiple sclerosis (MS). In fact, mouse models of demyelinating diseases have been useful in both the demonstration of T cell-mediated demyelination and in the characterization of the pathogenesis of immune-mediated demyelinating disease. EAE is a CD4 ⁺ T cell-mediated, demyelinating autoimmune disease of the CNS that is characterized by mononuclear cell infiltration.
Model of multiple sclerosis EAE can be induced by 2 different pathways. First pathway is the passive induction by the adoptive transfer of pre-activated myelin-specific T cells into naïve mice. Then the second pathway consists in injecting animals with a mixture of pathogens (CFA emulsion with antigens and PTX).

Administration of CFA/antigen emulsion is the most common way to induce EAE. Among them, different myelin protein epitopes can be used as antigens to induce EAE, such as myelin basic protein (MBP), Myelin oligodendrocyte glycoprotein (MOG) or proteolipid protein (PLP).

Discover our range of peptides for EAE induction