Cannabinoids May Reduce Alzheimer’s Proteins From Brain Cells

Summary: A new study finds THC reduces amyloid beta proteins in human neurons.

Source: Salk Institute.

Preliminary lab studies at the Salk Institute find THC reduces beta amyloid proteins in human neurons.

Salk Institute scientists have found preliminary evidence that tetrahydrocannabinol (THC) and other compounds found in marijuana can promote the cellular removal of amyloid beta, a toxic protein associated with Alzheimer’s disease.

While these exploratory studies were conducted in neurons grown in the laboratory, they may offer insight into the role of inflammation in Alzheimer’s disease and could provide clues to developing novel therapeutics for the disorder.

“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 Salk Professor David Schubert, the senior author of the paper.

Alzheimer’s disease is a progressive brain disorder that leads to memory loss and can seriously impair a person’s ability to carry out daily tasks. It affects more than five million Americans according to the National Institutes of Health, and is a leading cause of death. It is also the most common cause of dementia and its incidence is expected to triple during the next 50 years.

It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer’s disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the disease. But the precise role of amyloid beta and the plaques it forms in the disease process remains unclear.

In a manuscript published in June 2016’s Aging and Mechanisms of Disease, the Salk team studied nerve cells altered to produce high levels of amyloid beta to mimic aspects of Alzheimer’s disease.

The researchers found that high levels of amyloid beta were associated with cellular inflammation and higher rates of neuron death. They demonstrated that exposing the cells to THC reduced amyloid beta protein levels and eliminated the inflammatory response from the nerve cells caused by the protein, thereby allowing the nerve cells to survive.

“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 Antonio Currais, a postdoctoral researcher in Schubert’s laboratory and first author of the paper. “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.”

Brain cells have switches known as receptors that can be activated by endocannabinoids, a class of lipid molecules made by the body that are used for intercellular signaling in the brain. The psychoactive effects of marijuana are caused by THC, a molecule similar in activity to endocannabinoids that can activate the same receptors. Physical activity results in the production of endocannabinoids and some studies have shown that exercise may slow the progression of Alzheimer’s disease.

Image shows amyloid beta.
It has long been known that amyloid beta accumulates within the nerve cells of the aging brain well before the appearance of Alzheimer’s disease symptoms and plaques. Amyloid beta is a major component of the plaque deposits that are a hallmark of the disease. But the precise role of amyloid beta and the plaques it forms in the disease process remains unclear. NeuroscienceNews.com image is for illustrative purposes only.

Schubert emphasized that his team’s findings were conducted in exploratory laboratory models, and that the use of THC-like compounds as a therapy would need to be tested in clinical trials.

In separate but related research, his lab found an Alzheimer’s drug candidate called J147 that also removes amyloid beta from nerve cells and reduces the inflammatory response in both nerve cells and the brain. It was the study of J147 that led the scientists to discover that endocannabinoids are involved in the removal of amyloid beta and the reduction of inflammation.

About this neurology research article

Other authors on the paper include Oswald Quehenberger and Aaron Armando at the University of California, San Diego; and Pamela Maher and Daniel Daughtery at the Salk Institute.

Funding:The study was supported by the National Institutes of Health, The Burns Foundation and The Bundy Foundation.

Source: Salk Institute
Image Source: This NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids” by Antonio Currais, Oswald Quehenberger, Aaron M Armando, Daniel Daugherty, Pam Maher and David Schubert in Aging and Mechanisms of Disease. Published online June 23 2016 doi:10.1038/npjamd.2016.12

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Salk Institute. “Cannabinoids May Reduce Alzheimer’s Proteins From Brain Cells.” NeuroscienceNews. NeuroscienceNews, 29 June 2016.
<https://neurosciencenews.com/thc-amyloid-beta-alzheimers-4598/>.[/cbtab][cbtab title=”APA”]Salk Institute. (2016, June 29). Cannabinoids May Reduce Alzheimer’s Proteins From Brain Cells. NeuroscienceNews. Retrieved June 29, 2016 from https://neurosciencenews.com/thc-amyloid-beta-alzheimers-4598/[/cbtab][cbtab title=”Chicago”]Salk Institute. “Cannabinoids May Reduce Alzheimer’s Proteins From Brain Cells.” https://neurosciencenews.com/thc-amyloid-beta-alzheimers-4598/ (accessed June 29, 2016).[/cbtab][/cbtabs]


Abstract

Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids

The beta amyloid (Aβ) and other aggregating proteins in the brain increase with age and are frequently found within neurons. The mechanistic relationship between intracellular amyloid, aging and neurodegeneration is not, however, well understood. We use a proteotoxicity model based upon the inducible expression of Aβ in a human central nervous system nerve cell line to characterize a distinct form of nerve cell death caused by intracellular Aβ. It is shown that intracellular Aβ initiates a toxic inflammatory response leading to the cell’s demise. Aβ induces the expression of multiple proinflammatory genes and an increase in both arachidonic acid and eicosanoids, including prostaglandins that are neuroprotective and leukotrienes that potentiate death. Cannabinoids such as tetrahydrocannabinol stimulate the removal of intraneuronal Aβ, block the inflammatory response, and are protective. Altogether these data show that there is a complex and likely autocatalytic inflammatory response within nerve cells caused by the accumulation of intracellular Aβ, and that this early form of proteotoxicity can be blocked by the activation of cannabinoid receptors.

“Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids” by Antonio Currais, Oswald Quehenberger, Aaron M Armando, Daniel Daugherty, Pam Maher and David Schubert in Aging and Mechanisms of Disease. Published online June 23 2016 doi:10.1038/npjamd.2016.12

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  1. As research articles published in the lasts three ears shows , MARIJUANA USE CAN LEADS TO A TSUNAMI OF COGNITIVE IMPAIRMENTS AND AD and OTHERS DEMENTIAS.About the article above,published in the journal Neurology,did NOT shows None difference between the Placebo and Marijuana to calmars sh the patients. But for sure, the patients under Marijuana Use are in High Risk to HASTENS theirs Cognitive,Mood and Behavior Disorders by the Increase of Risk of BRAIN SHIRNKAGE CAUSED BY MARIJUANA IN THE ELDERLY PEOPLE. And as we can see bellow, scientific research articles Proved that Marijuana use (even once a week) can leads Teens,Adults, Middle Aged and Elderly NORMAL People, Directly to Cognitive Impairments and to Dementias. As we can see bellow,the researchers concluded that ” Using Marijuana Even ONCE a Week” can Leads to so SIGNIFICANT NEGATIVE EFFECTS ON THE BRAINS of Teenagers and Young Adults, including COGNITIVE DECLINE, POOR ATTENTION AND MEMORY, AND DECREASED OF SIX POINTS IN IQ, Leading to PERFORMS about 18 PERCENT WORSE on Long-Term Memory tests THAN young adults WHO NEVER USED marijuana.What’s more, the Longer they used the drug, the greater is the Hippocampus Shrinkage by Marijuana.
    And Brain Imaging (MRI and PET-SCAN) studies of regular MARIJUANA users have shown SIGNIFICANT SHRINKAGE OF THE BRAIN, ABNORMALITIES IN THE BRAIN’S GRAY MATTER, which is associated TO A REDUCTION IN INTELLIGENCE,nd the Brain Shrinkage (teens between 16″s and 19″s,was Permanent, REMAINED even after researchers controlled for major medical conditions, prenatal drug exposure, developmental delays and learning disabilities.Then using our Rational Thinking :: As MARIJUANA IT IS SO HARMFUL TO THE BRAINS of “normal” Teenagers and Young Persons,than, probably,the use of Marijuana can  deeply Increases the chances to Triggers and Hastens Mild Cognitive Impairmentsand AD and others Dementias in “NORMAL” persons in middle age , over 40 to 50 years, earlier and deeper.
    And as Marijuana cause Brain Shrinkage in young people , how HARMFUL CAN BE MARIJUANA TO THE “POOR BRAINS” OF AD and OTHERS DEMENTIA PATIENTS.It is a question of logic to governs with the support of it citizens to use the chance to STOPS the Risks of a Threatning “Pot” Cogninitive Impairment TSUNAMI.
    Based in (we can find by the title in Google) :
    1) Article published august 9,2014,with the title ,REGULAR MARIJUANA USE BAD FOR TEEN’S BRAINS about Public health Implications of Marijuana Legalization at the American Psychological Association’s 122nd Annual Convention
    2) American Journal Nature World News , in the article published in 12 March 2015 ,based in the research from Northwestern University , with the title : ”MARIJUANA USE MAY LEAD TO POOR LONG-TERM MEMORY”(Hippocampus shirnkage by “cannabis” includes Neurons, Axons and Astrocytes-complete Damage to Hippocampus).”MARIJUANA USE MAY LEAD TO POOR LONG-TERM MEMORY”,
    In the american journal Nature World News , in the article published in 12 March 2015 ,based in the esearch article of researchers from Northwestern University ,  with the title : ”MARIJUANA USE MAY LEAD TO POOR LONG-TERM MEMORY”,we can read that : 
    “ Marijuana use as a teenager may lead to Poor Long-Term Memory in one’s adult years, according to a new study. But researchers from NORTHWESTERN UNIVERSITY are among the first to not only Find that the HIPPOCAMPUS IS ABNORMALLY SHAPED IN HEAVY MARIJUANA USERS.And  Marijuana use it is also Directly Related to Poor Long-Term  Memory Performance (poor episodic memory-memory of our lives). It is the first time they’ve Found Solid Evidence of Their Suspicions.”The Memory processes that Is Affected by Marijuana are ones that we use every day to Solve Common Problems and to Sustain Our Relationships With Friends and Family,” senior author Dr. John Csernansky from Northwestern University said in a press release.ccording to the results, published in the journal Hippocampus, young adults who use Marijuana as teens, PERFORMED about 18 percent WORSE on Long-Term Memory tests THAN young adults WHO NEVER USED marijuana. What’s more, the Longer they used the drug, the greater the differences were in Hippocampus Shape ( Marijuana leads to Hippocampus Shrinkage).The Abnormal Shape Likely Reflects Damage to the Hippocampus and could Include the Structure’s Neurons, Axons or their supportive environments (Astrocytes).(That means a complete Damage to Hippocampus structures).” (from the site of the Nature World News) ;Impairment of memory, alteration of memory, disorders in motor coordination, in posture, impairments in cognitive ability, and disability in sensory perception.”( Looks like a patient with dementia ? But are “Some of the typical effects of Marijuana” in teens, adults, elderly patients …)

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