Is the secret of treating Alzheimer's, Parkinson's, Multiple Sclerosis hidden within the brain itself?
Alzheimer's, Parkinson's, and multiple sclerosis—all fatal diseases are related to inflammation in the brain. A permanent cure for these diseases has not yet been found. If we can identify the root cause of these illnesses, it would offer a ray of hope for those suffering from them. Some promising results have emerged from research conducted by senior scientists and other team members at the CSIR-Indian Institute of Toxicology Research (IITR), based in Lucknow, which is one of the premier institutes of CSIR.
Some significant facts have come to light that may potentially serve as a remedy in the future treatment of these severe diseases. Dr. Debabrata Ghosh, who is involved in this research, explained that there are factors hidden at the genetic level within the brain itself that contribute to fatal diseases like brain-related inflammation, Parkinson's, and Alzheimer's. However, some research findings have shown promising possibilities in the prevention of these diseases. Dr. Ghosh also revealed another important aspect emphasized in the research, which is related to arsenic. Studies have demonstrated how arsenic can be a contributing factor to such diseases.
Dr. Ghosh explained that he has discovered a microRNA, 'miRNA,' which can be instrumental in controlling inflammation in the brain. This RNA is notably small in size, measuring just 22 bases long. Dr. Ghosh's research has unveiled that a microRNA, known as miRNA-129-5P, suppresses the expression of the CD200R1 receptor protein, leading to inflammation in the brain.
While providing information about this receptor, Dr. Ghosh explained that the brain consists of various types of cells, including neurons, astrocytes, and oligodendrocyte cells. All of these are related to the central nervous system. However, microglia, also known as brain macrophages, are immune cells.
Singh et. al., J. Biol. Chem. (2022) 298(1) 101521
If any type of infection reaches the brain through pathogens, such as bacteria, microglia cells are responsible for destroying them. To eliminate these pathogens, these cells become active and form a barrier around the bacteria responsible for the infection, subsequently destroying them. During this process, several toxic elements, including reactive nitrogen species and oxygen species, are generated. Additionally, numerous soluble proteins, known as cytokines, are produced, aiding in the destruction of the pathogens.
According to Dr. Ghosh, when the infection or pathogen subsides, it is essential for the activity of microglia (immune cells) to return to a state of calm. Failure to do so can be detrimental to the body due to the toxins released by the active cells, which become more harmful and increase inflammation in the brain. Studies have revealed that the 'CD200R1' receptor can help bring them back to a calm state. This receptor is a protein within the microglia cells themselves. However, the challenge is that 'CD200R1' only functions when it binds or cross-links with a specific type of protein, known as 'CD200,' which is present in neurons."
The study observed that if this binding doesn't occur, the role of 'CD200R1' becomes insignificant, and microglia remain in an active state, causing harm to the body. The crucial point to consider is that for this process to be effective, the 'CD200R1' protein is necessary. Shedding light on how to maintain its essential role, Dr. Ghosh explained that various types of RNA are produced in the body, including messenger RNA (mRNA) and microRNA (miRNA). In the typical process, messenger RNA (mRNA) is synthesized from DNA, and proteins are subsequently produced from mRNA.
The entire process of making protein from messenger RNA is called protein synthesis. The process of making messenger RNA (mRNA) from DNA, which transmits genetic information to the next generation, is called transcription. In the study, the functioning of a microRNA (miRNA), specifically identified as miRNA-129-5P, was revealed. This microRNA binds to messenger RNA, disrupting the process of protein formation. This Interference occurs after the formation of messenger RNA (mRNA) from DNA, it hinders the subsequent protein formation. Specifically, it affects the same protein ‘CD200R1’ essential for calming microglia.
The second and most crucial aspect of the study involves the role of arsenic. Dr. Ghosh explained the connection between arsenic and serious diseases such as Parkinson's and Alzheimer's. The study revealed that arsenic doesn't decrease the activity of microglia because arsenic hinders the formation of 'CD200R1' protein. .
This is the same protein that forms a connection with 'CD200' and calms it. Arsenic increases the expression of a microRNA called miR-129-5p inhibiting the formation of the 'CD200R1' protein. To simplify how arsenic boosts miR-129-5p expression, Dr. Ghosh explained that when a gene is not supposed to be expressed, a cap is placed on it, preventing its activation.
This process is known as DNA methylation. Research has revealed that arsenic functions to remove this coating. Once the coating is removed, miR-129-5p starts to form through gene transcription. Consequently, the 'CD200R1' protein cannot be produced. In the absence of this protein, microglia cells are unable to return to a calm state, leading to increased inflammation in the brain. This inflammation can gradually progress to diseases like Parkinson's and Alzheimer's.
Important aspects of research
Expression of ‘CD200R1’ is essential for calming microglia cells.
A tiny microRNA, named miRNA-129-5P, obstruct the production of the 'CD200R1' protein thus preventing microglia cells from staying inactive.
Arsenic entering the human body via drinking water or any other source contributes to the creation of the problematic microRNA. This leads to the lack of 'CD200R1' protein essential for binding resulting in brain inflammation.
Which micro RNA hinders the formation of 'CD200R1', a protein that keeps microglia cells calm and how can its action be stopped? This has been identified.
By
Parul.Datt.Saxena
credit:
MicroRNA-129-5p-regulated microglial expression of the surface receptor CD200R1 controls neuroinflammation
Received for publication, December 2, 2021, and in revised form. December 12, 2021 Published, Papers in Press, December 22, 2021,
https://doi.org/10.1016/j.jbc.2021.101521
Vikas Singh, Shaivya Kushwaha, Jamal Ahmad Ansari, Siddhartha Gangopadhyay, Shubhendra K. Mishra, Rajib K. Dey, Ashok K. Giri, Satyakam Patnaik and Debabrata Ghosh
From the 'Immunotoxicology Laboratory, Food, Drug & Chemical Toxicology Group and Nanomaterial Toxicology Group, CSIR- Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India; Academy of Scientific and Innovative Research (ACSIR), Ghaziabad, India; Developmental Toxicology Laboratory, Systems Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow, Uttar Pradesh, India; "Molecular Genetics Division, CSIR-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata, West Bengal, India; "Water Analysis Laboratory, Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research, Lucknow, Uttar Pradesh, India