Blocking Protein, Reelin: a novel treatment strategy for multiple sclerosis

Blocking Protein, Reelin: a novel treatment strategy for multiple sclerosis
Sanaz Raeisi,^1,* Amirhossein Kheirkhah,²
1. Master of Medical Biotechnology, Department of Genetics, Shahid Sadoughi University of Medical Science, Yazd
2. Master of Medical Biotechnology, Department of Genetics, Shahid Sadoughi University of Medical Science, Yazd
Introduction: Multiple sclerosis is a neurological autoimmune disorder, affecting approximately more than 2.3 million people throughout the world. in MS, circulating immune cells penetrate into the CNS (the brain and spinal cord), where they wrongly attack myelin, the protective sheath that covers nerve fibers, and elevate inflammatory reactions, subsequently cause nerve cells to die. various therapies for MS, approved or in development, attempt to prevent immune cells from infiltrating the CNS to cease neuroinflammation, demyelination (loss of myelin), and disease progression. however, serious side effects are known with most of these approved therapies, emphasizing a need for better and safer immunomodulatory approaches. Reelin is a key protein secreted from brain and some other organs and has function on brain development, neural connection during adulthood, and also act on endothelial cells (those lining blood cells), regulating the adhesion and passage of monocytes to and through the endothelium consequently regulates how permeable blood vessels are to immune cells. this suggests decreasing the amount of this protein significantly protected against development of the disease’s characteristic symptoms and promoted recovery in multiple sclerosis. The findings could lead to a new treatment strategy for this neurological disease and other conditions marked by chronic inflammation. This study attempts to review related researches.
Methods: Multiple sclerosis(MS) is a demyelinating disease in which the insulating covers of nerve cells in the brain and spinal cord are damaged. Interrupt in the ability of parts of the nervous system to transmit signals, resulting in a range of signs and symptoms, including physical, mental, and sometimes psychiatric problems. In the meantime, there is a great need for a treatment that covers a wide spectrum of MS. Reelin is a key. initially, it recognized only for its role in guiding neurons during brain development and as a synaptic homeostatic regulatory. Recently reported non-neuronal function for systemically circulating Reelin in the vasculature, where Reelin regulates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-B)–mediated expression of several vascular adhesion molecules. findings revealed that circulating Reelin promoted the vascular inflammatory response by increasing leukocyte-endothelial cell adhesion and the increased expression of mRNAs encoding endothelial adhesion molecules. examining blood concentrations of Reelin in patients with relapsing-remitting MS (the most common form of the disease), scientists found that while Reelin concentrations were about the same in patients in remission as those without the disease, concentrations were elevated in patients during relapse. Investigating further, scientists worked with mice affected by a disease called experimental autoimmune encephalomyelitis (EAE), a condition that mimics human MS. these animals were genetically modified so that the researchers could control Reelin production and some cases received antibodies against circulating Reelin using immunodepletion procedure.
Results: Findings reveal that eliminating Reelin substantially mitigated the disease's typical paralysis or even eliminated it altogether, in contrast to mice with normal Reelin levels. These effects appeared to originate the lack of monocyte adhesion on the altered animals' blood vessel walls, which inhibit entry into the central nervous system. Reelin appears to regulate the production of adhesion molecules on blood vessel walls that capture circulating monocytes. When the scientists decreased Reelin in animal models, levels of these adhesion molecules also declined, preventing them from capturing monocytes and causing inflammation. This strategy was even effective in animals that already displayed symptoms of the disease -- a situation that more closely mimics human patients diagnosed with MS -- reducing paralysis severity and promoting healing.
Conclusion: MS, a disease for which several effective drugs exist that nevertheless can have significant side effects .these findings suggest that circulating Reelin levels might correlate with MS severity and stages, and that lowering levels of Reelin may be a novel way to treat MS. some suggest that reducing immune cells' ability to accumulate and cause inflammation by altering Reelin levels could represent a new strategy for treating patients with MS. wondering if Reelin plays a similar role in other inflammatory diseases. MS, a disease for which several effective drugs exist that nevertheless can have significant side effects .these findings suggest that circulating Reelin levels might correlate with MS severity and stages, and that lowering levels of Reelin may be a novel way to treat MS. some suggest that reducing immune cells' ability to accumulate and cause inflammation by altering Reelin levels could represent a new strategy for treating patients with MS. wondering if Reelin plays a similar role in other inflammatory diseases.
Keywords: Multiple sclerosis, reelin, inflammation