Looking at it the other way round, disabling CB2 receptors might be bad in HD. Knowing this, and knowing that the immune system is overactive in Huntington’s disease, activating CB2 receptors ought to be a good thing. Activating CB2 receptors ‘calms down’ these immune cells, causing them to produce less of their own signalling chemicals - the cytokines we mentioned earlier. One interesting thing about CB2 receptors is that they are mostly found on cells of the immune system. But - just so we’re clear - this isn’t a study of cannabis! They’re called that because they can be triggered by the chemicals in cannabis.
That’s how each cell in our body is able to respond appropriately to a variety of signals.ĬB2 receptors are part of the ‘cannabinoid’ receptor family. When that happens, the receptor triggers a series of chemical events inside the cell, eventually changing the cell’s behavior.Įach receptor is only capable of ‘catching’ a particular type of signalling chemical, and each receptor causes its own series of events in the cell. CB2 receptors?Ī receptor is a molecule that sticks out of a cell, waiting for a signalling chemical to reach it. And with a new paper in the Journal of Neuroscience, Muchowski’s team has done it again - this time with a remarkable study centering on the activity of ‘CB2 receptors’ in the immune system. So, studying the immune system to understand HD, and as a target for possible treatments, is a bit of a hot topic right now. And earlier this year, Muchowski’s team reported that transplanting bone marrow from ‘normal’ mice into HD mice was mildly beneficial. Last year, a group of researchers led by Dr Paul Muchowski at the Gladstone Institute of Neurological Disease in California showed that altering the chemical behavior of white blood cells, using a drug called JM6, made HD mice live longer. But there are already signs that artificially altering the immune system might be one way to fight HD. The links between the HD gene, the behavior of the immune system and the brain are still being worked out. And white blood cells from HD patients are hyperactive - when they’re grown in the lab and fired up using chemicals from bacteria, they churn out more cytokines than normal. On average, levels of immune signaling chemicals called cytokines are higher than normal in people with the Huntington’s disease mutation, even before symptoms begin. One discovery that’s arisen from this whole-body approach is that the immune system - our defense against infection and injury - seems to behave slightly differently in HD patients. Image credit: Society for Neuroscience (Bouchard et al.) The other lines are groups of ‘control’ mice. The ‘GW’ line doesn’t drop at all during the trial.
Each time a mouse dies, the line drops down. This graph shows the effect of GW on the survival of R6/2 mice. But the mutant huntingtin protein that causes HD is produced by every cell in the body, and in recent years, researchers have been looking beyond the brain in the search for HD treatments. Huntington’s disease is called a neurodegenerative disease, because most of the symptoms are caused by the malfunctioning and death of neurons.
Now, a drug that activates CB2 receptors on immune cells has been shown to improve symptoms and survival in HD mice - with interesting implications for the immune system as a target for HD therapies. The immune system is thought to behave abnormally in Huntington’s disease. By Professor Ed Wild DecemEdited by Dr Jeff Carroll
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