Scientists discover 'molecular switch' that can help repair damage to central nervous system

The role of myelin is similar to that of an insulator surrounding a wire, it preserves the electrical signals transmitted across the nervous system

One of the biggest challenges in the treatment of neurological disorders such as Alzheimer's disease is irreversible neural damage. However, a study by researchers from Mayo clinic claims that a molecular switch with the ability to 'turn on' the substance that can help in healing this damage has been discovered.

According to the study, when the receptor known as Protease Activated Receptor 1 (PAR1)—which is activated by the blood protein, Thrombin—is genetically switched off—the body acquires the ability to regenerate a fatty substance called myelin, that covers and protects nerves.

"Myelin regeneration holds tremendous potential to improve function. We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system does have a good capacity for innate repair," said Isobel Scarisbrick, senior author of the study, in a statement.

Myelin and its role in the central nervous system

Representational Picture Pixabay

The role of myelin is similar to that of an insulator surrounding a wire. It preserves the electrical signals transmitted across the nervous system. However, certain conditions can affect the function of myelin. One such condition is known as Demyelination.

It is the damage to the myelin sheath or covering around nerves. This disrupts the flow of electrical signals between neurons, causing loss of motor and sensory functions. It is characteristic of neurological disorders such as schizophrenia, Alzheimer's disease, multiple sclerosis, Huntington's disease, and injuries to the spinal cord.

PAR1 is a receptor that is found on the surface of cells. However, the excess of a blood protein known a Thrombin, which is associated with the process of healing, triggers PAR1. This leads to a stoppage in the production of myelin. Oligodendrocyte progenitor cells (OPCs), that are responsible for the regeneration of myelin, can be found at the location of a myelin injury, which also includes demyelinating injuries in multiple sclerosis.

"These oligodendroglia fail to differentiate into mature myelin regenerating cells for reasons that remain poorly understood," said Scarisbrick.

Mouse models to understand the action of PAR1

Two mouse models were employed by the researchers for the study. One model focussed on myelin injury. The other focussed on studying chronic demyelination; with emphasis on individual modelling to take into account the unique traits of myelin loss in different neurological disorders. In order to block the action of excess thrombin, the scientists genetically deactivated PAR1.

human brain

Discovery of a new neurological interaction

Firstly, the researchers discovered a new molecular switch that initiated the regeneration of myelin. Secondly, and most importantly, they discovered a new interaction between PAR1 receptor and a powerful growth system called brain-derived neurotropic factor (BDNF). BDNF is important for the maintenance of brain cells and promotes their health, functions, and growth.

Additionally, the authors also found that a drug approved by the Food and Drug Administration(FDA) that impedes the function of the PAR1 receptor, also had the potential to promote the production of myelin in cells that were tested in the laboratory.

What is the next step for the study?

Despite the findings suggesting that understanding this process can help devise methods to treat several neurological disorders, it is far from clinical trials. Further research to verify and advance the findings is required say the authors as the study has been tested only under laboratory conditions.

"We have not used the drug in animals yet, and it is not ready to put in patients for the purpose of myelin repair. Using cell culture systems, we are showing that this has the potential to improve myelin regeneration," concluded Scarisbrick.

This article was first published on January 12, 2020