Researchers have discovered a molecular switch that has the ability to turn on a substance in animals that is capable of repairing neurological damages in disorders such as multiple sclerosis (MS) by switching off a receptor activated by blood proteins called Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin – a fatty substance that protects and coats nerves. Repair of the central nervous system (CNS) constitutes an integral part in treating neurologic diseases and plays a crucial role in restoring CNS structure and function. Pronounced strategies have been developed to reconstruct the damaged neural tissue tested preclinically in various animal models. Researchers have used the genetic pathway to block PAR1, which in turn blocks the action of excess thrombin.
Myelin functions as a wire insulator that protects electrical signals sent via the nervous system. Injury to the myelin or demyelination slows electrical signals between brain cells, resulting in the loss of sensory and the motor function. Sometimes the damage caused becomes permanent. Demyelination is mainly found in disorders such as MS, Alzheimer's disease, schizophrenia, Huntington's disease, and spinal cord injury. Thrombin is a protein present in blood that aids in healing. The presence of a larger amount of thrombin triggers PAR1 receptor – found on the surface of cells, blocks myelin production. Oligodendrocyte progenitor cells are capable of myelin regeneration which are often found at sites of myelin injury, including demyelinating injuries in multiple sclerosis.
Research identifies PAR1 as a molecular switch for myelin regeneration. Blocking the function of the PAR1 – the thrombin receptor promotes myelin regeneration in two unique experimental models of demyelinating disease. A global knockout of the thrombin receptor PAR1 accelerates myelin development. The findings in the future will help in the development of treatments for diseases associated with demyelination, like multiple sclerosis. Myelin regeneration holds the potential to improve the function of the central nervous system. Studies revealed that when the PAR1 receptor is blocked, neurological healing is much proper and occurs more quickly. Certain research found that since the nervous system does have a good capacity for innate repair, it sets the platform for the development of new clinically relevant myelin regeneration strategies.
The N-methyl-D-aspartate (NMDA) receptor – a principal subtype of glutamate receptor mediating fast excitatory transmission at the junction of synapses in the dorsal horn of the spinal cord and also found on the other regions of the central nervous system. NMDA receptors are vital for the lasting enhancement of synaptic transmission that occurs both physiologically and in pathological conditions. Evidence indicates that the protein tyrosine kinase, Src, that regulates the activity of NMDA receptors. It has been discovered that, up-regulation of the NMDA receptor function, leads to activation of Src that mediates the induction of the lasting enhancement of excitatory transmission known as long-term potentiation in the CA1 region of the hippocampus. Src amplifies the up-regulation of NMDA receptor function – produced by raising the intracellular concentration of sodium.
The research discovered a new molecular switch that turns on myelin regeneration and also discovered a new interaction between PAR1 receptor and an immensely powerful growth system. It is also mentioned as brain-derived neurotropic factor (BDNF). BDNF functions as a fertilizer for brain cells that keeps them healthy, functioning, and growing. Recently, FDA-approved drug that inhibits the PAR1 receptor shows the ability to improve myelin production in cells tested in the laboratory. The boost in the NMDA receptor function produced by the coincidence of activating Src and raising the intracellular sodium is a crucial factor in the pathophysiological and physiological enhancement of excitatory transmission in the dorsal horn of the spinal cord and elsewhere in the central nervous system.