Scientists have built a map of the toxic immune cells that contribute to neurodegeneration in multiple sclerosis (MS). Their findings may open the door to the development of new medications that protect the brain from the effects brought on by these harmful immune cells.
Results were reported in the study, “Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation,” published in the journal Nature Immunology.
Neurodegeneration is the central hallmark of many inflammatory and neurological disorders, including MS, amyotrophic lateral sclerosis (ALS), Alzheimer’s, and Parkinson’s disease. Oxidative stress, a phenomenon in which cells are progressively damaged due to the presence of high levels of oxidant molecules, or reactive oxygen species (ROS), is one of the contributors to neurodegeneration.
In the case of MS, it has been shown that microglia — cells that support and protect neurons, and are considered the immune cells of the brain — produce large amounts of ROS that contribute to oxidative stress during the early phases of the disease, resulting in progressive brain damage. However, it was not known how immune cells controlled the production of these toxic compounds.
Now, investigators at Gladstone Institutes and their collaborators developed a technique that enables them to track when specific immune cells, which are known to produce large amounts of ROS in the central nervous system (CNS, the brain and spinal cord), activate certain genes, including those that could be involved in the production of ROS.
The new method, called Tox-seq, combines single-cell RNA-sequencing technology with a labeling technique that allows researchers to track specific types of ROS-producing immune cells, and at the same time know which genes are being “switched on” or “off” at specific time intervals.
(Note: RNA-sequencing is a technique that allows scientists to examine all RNA molecules produced from active genes in a cell or tissue.)
When applied to mice with experimental autoimmune encephalomyelitis (EAE) — a disease that mimics MS in humans — Tox-seq allowed researchers to build a map containing the genetic signature of all immune cells that contributed to the buildup of toxic ROS in the animals’ CNS.
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