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sciencealert.com
Thursday 30 June 2016
Marijuana compound removes
toxic Alzheimer's protein
from brain
An active compound in marijuana called tetrahydrocannabinol (THC) has been found to promote the removal of toxic clumps of amyloid beta protein in the brain, which are thought to kickstart the progression of Alzheimer's disease.
The finding supports the results of previous studies that found evidence of the protective effects of cannabinoids, including THC, on patients with neurodegenerative disease.
"Although other studies have offered evidence that cannabinoids might be neuroprotective against the symptoms of Alzheimer's, we believe our study is the first to demonstrate that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells," says David Schubert from the Salk Institute for Biological Studies in California.
Schubert and his colleagues tested the effects of THC on human neurons grown in the lab that mimic the effects of Alzheimer's disease.
THC is not only responsible for the majority of marijuana's psychological effects -- including the high -- thanks to its natural pain-relieving properties, it’s also been touted as an effective treatment for the symptoms of a variety of diseases/disorders from HIV and chemotherapy to chronic pain, post traumatic stress disorder, and stroke.
Researchers are working on breeding genetically modified yeast that can produce THC more efficiently than it would be to make synthetic versions.
The compound works by passing from the lungs to the bloodstream, where it attaches to two types of receptors, cannabinoid receptor (CB) 1 and 2, which are found on cell surfaces all over the body.
In the brain, these receptors are most concentrated in neurons associated with pleasure, memory, thinking, coordination and time perception, and usually bind with a class of lipid molecules called endocannabinoids produced by the body during physical activity to promote cell-to-cell signalling in the brain.
Over the years, research has suggested that by binding to these receptors, THC could be having another effect on ageing brains, because it appears to helps the body clear out the toxic accumulations -- or 'plaques' -- of amyloid beta.
No one is entirely sure what causes Alzheimer’s disease, but it is thought to result from a build-up of two types of lesions: amyloid plaques and neurofibrillary tangles.
Amyloid plaques sit between the neurons as dense clusters of beta-amyloid molecules -- a sticky type of protein that easily clumps together -- and neurofibrillary tangles are caused by defective tau proteins that clump up into a thick, insoluble mass in the neurons.
It’s not clear why these lesions begin to appear in the brain, but studies have linked inflammation in the brain tissue to the proliferation of plaques and neurofibrillary tangles. So if we can find something that eases brain inflammation while at the same time encourages the body to clear out these lesions, we could be on the way to finding the first effective treatment for Alzheimer’s.
In 2006, researchers at the Scripps Research Institute found that THC inhibits the formation of amyloid plaques by blocking the enzyme in the brain that produces them, and now Schubert and his team have demonstrated that it can also eliminate a dangerous inflammatory response from the nerve cells, ensuring their survival.
"Inflammation within the brain is a major component of the damage associated with Alzheimer's disease, but it has always been assumed that this response was coming from immune-like cells in the brain, not the nerve cells themselves," says study member Antonio Currais.
"When we were able to identify the molecular basis of the inflammatory response to amyloid beta, it became clear that THC-like compounds that the nerve cells make themselves may be involved in protecting the cells from dying."
So far this phenomenon has only been demonstrated in neurons in the lab. The next step will be for Schubert and his team to observe the link between THC and reduced inflammation and plaque build-up in a clinical trial. They have reportedly found a drug candidate called J147 that appears to have the same effects as THC, so they may be able to test the effects of THC without the U.S. federal government's forbidding such tests.
The results have been published in "Aging and Mechanisms of Disease."
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