“The endocannabinoids and their attending cannabinoid (CB)(1) receptors have been implicated in the control of cognition, but their possible roles in dementias are still unclear.
The results suggest that an Aβ(42)-dependent impairment in brain anandamide mobilization contributes to cognitive dysfunction in AD.”
“Cleavage of the amyloid precursor protein (APP) by gamma-secretase generates a neurotoxic amyloid beta-peptide (Abeta) that is thought to be associated with the neurodegeneration observed in Alzheimer’s disease (AD) patients. Presenilin is the catalytic member of the gamma-secretase proteolytic complex and mutations in presenilins are the major cause of early-onset familial Alzheimer’s disease. In addition to APP, gamma-secretase substrates include Notch1 homologues, Notch ligands Delta and Jagged, and additional type I membrane proteins, raising concerns about mechanism-based toxicities that might arise as a consequence of inhibiting gamma-secretase. Notch signaling is involved in tumorigenesis as well as in determining the fates of neural and nonneural cells during development and in adults. Alterations in proteolysis of the Notch by gamma-secretase could be involved in the pathogenesis of AD. Inconsistently, several recent observations have indicated that enhanced Notch signaling and expression could be instrumental in neurodegeneration in AD. Therefore, detailed and precise study of Notch signaling in AD is important for elucidating diverse mechanisms of pathogenesis and potentially for treating and preventing Alzheimer’s disease.”
“Aberrant Notch signaling has recently emerged as a possible mechanism for the altered neurogenesis, cognitive impairment, and learning and memory deficits associated with Alzheimer disease (AD). Recently, targeting the endocannabinoid system in models of AD has emerged as a potential approach to slow the progression of the disease process. Although studies have identified neuroprotective roles for endocannabinoids, there is a paucity of information on modulation of the pro-survival Notch pathway by endocannabinoids. In this study the influence of the endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol, on the Notch-1 pathway and on its endogenous regulators were investigated in an in vitro model of AD. We report that AEA up-regulates Notch-1 signaling in cultured neurons… In summary, AEA has the proclivity to enhance Notch-1 signaling in an in vitro model of AD, which may have relevance for restoring neurogenesis and cognition in AD.”
“The role of the endocannabinoid system in several diseases is currently under intense study. Among these, Alzheimer’s disease may be a new promising area of research. We have recently reported the existence of profound changes in the location and density of several elements of this system in Alzheimer’s disease tissue samples, indicating that a non-neuronal endocannabinoid system is up-regulated in activated glia. Additional data from other groups suggest that glial cells may be important elements in the regulation of endocannabinoid system activity, both in health as in disease. Some of these aspects are briefly discussed in the present review.”
“‘Clearly in the test tube cannabinoids have the ability to block at least one of the probable causal mechanisms in Alzheimer’s disease and so become a potential treatment or preventative agent that needs to be tested in humans.”
Dr Richard Harvey, research director of the Alzheimer’s Society
Read more: http://www.alzheimers.org.uk/site/scripts/news_article.php?newsID=123
“For those who have inhaled, there may be some good news: Marijuana use may cut the risk of developing Alzheimer’s disease by reducing inflammation in the brain…
The findings may explain studies showing those who regularly used marijuana in the 1960s and 1970s are now less likely to develop Alzheimer’s disease than their non-smoking contemporaries.
Under a National Institutes of Health grant, researchers used a synthetic drug similar to marijuana to treat rats with brain inflammation typically associated with Alzheimer’s disease, a form of dementia that afflicts 4.5 million people in the United States alone.”
Read more: http://dsc.discovery.com/news/2006/10/19/marijuana_hea.html
The findings showed that “cannabinoids work both to prevent inflammation and to protect the brain,” says researcher Maria de Ceballos in a news release. That “may set the stage for [cannabinoids’] use as a therapeutic approach for [Alzheimer’s disease].”
The cannabinoids completely prevented activation of cells that trigger inflammation. These cells gather near plaque and are believed to be involved in the development of Alzheimer’s disease.
“Our results indicate that cannabinoid receptors are important in the pathology of Alzheimer’s disease and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease,” write the researchers in the journal.”
Read more: http://www.webmd.com/alzheimers/news/20050223/marijuana-ingredient-may-help-alzheimers
“Although our study is far from final, it does show that there is a previously unrecognized molecular mechanism through which THC may directly affect the progression of Alzheimer’s disease.”
“THC and its analogs may provide an improved [treatment for] both the symptoms and progression of Alzheimer’s disease,” the researchers conclude”
Read more: http://www.webmd.com/alzheimers/news/20061006/marijuana-may-slow-alzheimers
Good news for aging hippies: smoking pot may stave off Alzheimer’s disease.
New research shows that the active ingredient in marijuana may prevent the formation of deposits in the brain associated with the degenerative disease.
Researchers at the Scripps Research Institute in California found that marijuana’s active ingredient, delta-9-tetrahydrocannabinol, or THC, can prevent an enzyme called acetylcholinesterase from accelerating the formation of “Alzheimer plaques” in the brain more effectively than commercially marketed drugs.
THC is also more effective at blocking clumps of protein that can inhibit memory and cognition in Alzheimer’s patients, the researchers reported in the journal Molecular Pharmaceutics.
The researchers said their discovery could lead to more effective drug treatment for Alzheimer’s, the leading cause of dementia among the elderly.
Those afflicted with Alzheimer’s suffer from memory loss, impaired decision-making, and diminished language and movement skills. The ultimate cause of the disease is unknown, though it is believed to be hereditary.
Marijuana is used to relieve glaucoma and can help reduce side effects from cancer and AIDS treatment.”
“THC, the key compound in marijuana, may also be the key to new drugs for Alzheimer’s disease. That’s because the marijuana compound blocks the formation of brain-clogging Alzheimer’s plaques better than current Alzheimer’s drugs….
these findings offer convincing evidence that THC possesses remarkable inhibitory qualities, especially when compared to [Alzheimer’s drugs] currently available to patients,” Janda says in a news release.
“Although our study is far from final, it does show that there is a previously unrecognized molecular mechanism through which THC may directly affect the progression of Alzheimer’s disease.”
Janda’s team found that THC blocks an enzyme called acetylcholinesterase, which speeds the formation of amyloid plaque in the brains of people with Alzheimer’s disease.
The Alzheimer’s drugs Aricept and Cognex work by blocking acetylcholinesterase. When tested at double the concentration of THC, Aricept blocked plaque formation only 22 percent as well as THC, and Cognex blocked plaque formation only 7 percent as well as THC.
“THC and its analogs may provide an improved [treatment for] both the symptoms and progression of Alzheimer’s disease,” the researchers conclude.”
Read more: http://www.cbsnews.com/2100-500368_162-2072101.html