Caffeine among compounds that could combat dementia

For years we have seen studies noting observational connections between consumption of coffee and reduced risk of dementia, but it's only been recently that scientists have started to drill down into the neurological reasons underpinning these observations. A new study by Indiana University researchers has revealed how several compounds, including caffeine, help boost the production of an enzyme that has been shown to protect the brain against several degenerative neurological disorders.

In previous research, the team discovered that an enzyme known as NMNAT2 was shown to reduce the cognitive defects associated with dementia and other degenerative brain diseases. The enzyme does this by combatting tau, which are misfolded proteins that can build up as plaques in the brain as we age and have been linked to numerous neurodegenerative disorders, including Alzheimer's, Parkinson's and Huntington's diseases and ALS (aka Lou Gehrig's disease). The enzyme also protects neurons from stress.

Their most recent research looked at what specific compounds affected production of the NMNAT2 enzyme in the brain, both in increasing and decreasing its presence. Screening over 1,280 compounds they identified 24 substances that boosted the production of the NMNAT2 enzyme as well as noting an additional 13 compounds that had the potential to lower the enzyme's production.

The two most significant compounds noted in their research as boosting NMNAT2 enzyme production were caffeine and rolipram, the latter being a discontinued drug originally used as an antidepressant in the mid-1990s. 

Honing in on the effects of caffeine, the researchers administered the compound to mice that had been modified to produce lower levels of NMNAT2. After the administration of caffeine, these modified mice were shown to begin producing levels of the enzyme similar to those found in normal mice. 

"This work could help advance efforts to develop drugs that increase levels of this enzyme in the brain, creating a chemical 'blockade' against the debilitating effects of neurodegenerative disorders," reported Professor Hui-Chen Lu, one of the lead authors of the study.

Several observational studies in recent years have noted a correlation between moderate coffee consumption and lower instances of dementia, but there have been notable inconsistencies in the results. The effect of other lifestyle factors and the variance in how people consume caffeine has resulted in many meta-studies reaching inconclusive results when trying to ascertain a clear correlation between caffeine intake and lowered cognitive decline.

By drilling down into what the specific triggers are that produce this protective enzyme in the brain, researchers hope to gain better insights into the processes behind degenerative neurological disorders. 

"Increasing our knowledge about the pathways in the brain that appear to naturally cause the decline of this necessary protein is equally as important as identifying compounds that could play a role in future treatment of these debilitating mental disorders," Professor Lu explains.

So non-coffee drinking senior citizens aren't urged to take up the habit just yet, but scientists are slowly unlocking more pieces in the puzzle of how to better combat the rising number of neurodegenerative disorders striking the minds of millions.

The team's research was published in the journal Scientific Reports.


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