Most multiple sclerosis (MS) drugs work by weakening the inflammatory response of the disease-induced immune response. They are good at controlling acute relapse, but not very effective at stopping disease progression and neurodegeneration. And control of the immune system can leave patients vulnerable to serious opportunistic infections.
Scientists at the Karolinska Institute in Sweden are now focusing on microglia, which are immune cells that constantly remove unwanted cell debris from the central nervous system in processes related to autophagy. This is the process of cleaning up or recycling components with damaged cells.
Trehalose, a naturally occurring sugar in plants and fungi, enhances the cleansing function of microglia, leading to MS remission in mice, the team reported in a new study published. Scientific immunology..
“This not only uses these findings as a treatment for established diseases, but also offers the potential for aggressive dietary recommendations,” said Rasmus Berglund, the first author of the study. Said in.
Earlier, Berglund et al. Established a link between an autophagy-related protein called Atg7 and the severity of the disease in a mouse model of MS. Later, researchers decided to study microglia Atg7.
Accidental attack on the protective myelin sheath around the nerve to remove the Atg7 gene in T cells that causes MS did not affect clinical disease. However, the team found that removing it with microglia impaired the cell’s ability to remove debris, causing persistent neuroinflammation that lacked the convalescent phase seen in control mice. Microglia without Atg7 showed reduced debris uptake and degradation.
Since age is the strongest risk factor for progressive MS, the team compared the effects of Atg7 deletion with the effects of aging. Interestingly, there were many similarities between Atg7-deficient microglia and aged mouse microglia. Both of them showed altered gene expression that was associated with the progression of MS disease and showed similar clinical signs.
Based on these findings, researchers believed that increasing microglial autophagy could have beneficial effects on MS. They chose trehalose, which is known to induce autophagy. Treatment of aged mice one week before MS induction increased clearance of myelin debris by microglia and improved the severity of MS, the team reported.
Microglia have been extensively studied for their role in neurodegenerative diseases. A team led by Mount Sinai Medical College recently discovered that microglia can sense and suppress excessive neuronal activation. Therefore, it can play a role in managing behavioral problems such as attacks of neurodegenerative diseases.
Another team at Stanford University Identified B cell receptor CD22 as a negative regulator of microglial function. Blocking CD22 with aged mouse antibodies was more effective at removing myelin debris than control antibodies. It also removed beta-amyloid and alpha-synuclein, which accumulate in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.
Berglund et al. Believe that their findings provide new insights into how microglia can restore CNS stability by removing debris produced by inflammation. “Treatment with trehalose has shown that microglial cells can target beneficial purposes with compounds already found in plant and fungal diets (and therefore may not be toxic),” he said in a statement. Stated.
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