Caffeine boosts enzyme that could protect against dementia, study finds

March 7, 2017
Indiana University scientists have identified 24 compounds that increase the brain's production of the enzyme NMNAT2, which helps prevent the formation of these tangles associated with neurodegenerative disorders such as Alzheimer's disease. Credit: National Institute on Aging/National Institutes of Health

A study by Indiana University researchers has identified 24 compounds—including caffeine—with the potential to boost an enzyme in the brain shown to protect against dementia.

The protective effect of the , called NMNAT2, was discovered last year through research conducted at IU Bloomington. The new study appears today in the journal Scientific Reports.

"This work could help advance efforts to develop drugs that increase levels of this enzyme in the , creating a chemical 'blockade' against the debilitating effects of neurodegenerative disorders," said Hui-Chen Lu, who led the study. Lu is a Gill Professor in the Linda and Jack Gill Center for Biomolecular Science and the Department of Psychological and Brain Sciences, a part of the IU Bloomington College of Arts and Sciences.

Previously, Lu and colleagues found that NMNAT2 plays two roles in the brain: a protective function to guard neurons from stress and a "chaperone function" to combat misfolded proteins called tau, which accumulate in the brain as "plaques" due to aging. The study was the first to reveal the "chaperone function" in the enzyme.

Misfolded proteins have been linked to neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, as well as , also known as ALS or Lou Gehrig's disease. Alzheimer's disease, the most common form of these disorders, affects over 5.4 million Americans, with numbers expected to rise as the population ages.

To identify substances with the potential to affect the production of the NMNAT2 enzyme in the brain, Lu's team screened over 1,280 compounds, including existing drugs, using a method developed in her lab. A total of 24 compounds were identified as having potential to increase the production of NMNAT2 in the brain.

One of the substances shown to increase production of the enzyme was caffeine, which also has been shown to improve memory function in mice genetically modified to produce high levels of misfolded tau proteins.

Lu's earlier research found that mice altered to produce misfolded tau also produced lower levels of NMNAT2.

To confirm the effect of caffeine, IU researchers administered caffeine to mice modified to produce lower levels of NMNAT2. As a result, the mice began to produce the same levels of the enzyme as normal mice.

Another compound found to strongly boost NMNAT2 production in the brain was rolipram, an "orphaned drug" whose development as an antidepressant was discontinued in the mid-1990s. The compound remains of interest to brain researchers due to several other studies also showing evidence it could reduce the impact of tangled proteins in the brain.

Other compounds shown by the study to increase the production of NMNAT2 in the brain—although not as strongly as caffeine or rolipram—were ziprasidone, cantharidin, wortmannin and . The effect of retinoic acid could be significant since the compound derives from vitamin A, Lu said.

An additional 13 compounds were identified as having potential to lower the production of NMNAT2. Lu said these compounds are also important because understanding their role in the body could lead to new insights into how they may contribute to dementia.

"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," she said.

Explore further: Brain study suggests new ways to protect against neurodegeneration

More information: Yousuf O. Ali et al, Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons, Scientific Reports (2017). DOI: 10.1038/srep43846

Related Stories

Brain study suggests new ways to protect against neurodegeneration

June 2, 2016
A study led by biomedical researchers at Indiana University has found evidence that an enzyme known as NMNAT2 may help protect against the debilitating effects of certain degenerative brain diseases, including Alzheimer's.

Improving brain's garbage disposal may slow Alzheimer's and other neurodegenerative diseases

December 21, 2015
A drug that boosts activity in the brain's "garbage disposal" system can decrease levels of toxic proteins associated with Alzheimer's disease and other neurodegenerative disorders and improve cognition in mice, a new study ...

Supercharged sprout vitamin inspiration for new Alzheimer's drug research

December 23, 2016
A supercharged version of the acid derived from our Christmas dinner veg is the basis of new research aimed at developing a new drug to treat Alzheimer's disease.

Aging brains need 'chaperone' proteins

January 30, 2014
(Medical Xpress)—The word "chaperone" refers to an adult who keeps teenagers from acting up at a dance or overnight trip. It also describes a type of protein that can guard the brain against its own troublemakers: misfolded ...

Researchers report promising new Alzheimer's drug

November 3, 2016
A new experimental treatment against Alzheimer's has proved to be promising and free of harmful side effects, researchers in the United States reported Wednesday.

Animal study shows how exercise may energize brain cell function

November 19, 2015
As we age or develop neurodegenerative diseases such as Alzheimer's , our brain cells may not produce sufficient energy to remain fully functional. Researchers discovered that an enzyme called SIRT3 that is located in mitochondria—the ...

Recommended for you

Lifestyle changes to stave off Alzheimer's? Hints, no proof

July 20, 2017
There are no proven ways to stave off Alzheimer's, but a new report raises the prospect that avoiding nine key risks starting in childhood just might delay or even prevent about a third of dementia cases around the world.

Blood test identifies key Alzheimer's marker

July 19, 2017
A new study led by researchers at Washington University School of Medicine in St. Louis suggests that measures of amyloid beta in the blood have the potential to help identify people with altered levels of amyloid in their ...

Steering an enzyme's 'scissors' shows potential for stopping Alzheimer's disease

July 19, 2017
The old real estate adage about "location, location, location" might also apply to the biochemical genesis of Alzheimer's disease, according to new research from the University of British Columbia.

Brain scans may change care for some people with memory loss

July 19, 2017
Does it really take an expensive brain scan to diagnose Alzheimer's? Not everybody needs one but new research suggests that for a surprising number of patients whose memory problems are hard to pin down, PET scans may lead ...

Can poor sleep boost odds for Alzheimer's?

July 18, 2017
(HealthDay)— Breathing problems during sleep may signal an increased risk for Alzheimer's disease, a trio of studies suggests.

Hearing is believing: Speech may be a clue to mental decline

July 17, 2017
Your speech may, um, help reveal if you're uh ... developing thinking problems. More pauses, filler words and other verbal changes might be an early sign of mental decline, which can lead to Alzheimer's disease, a study suggests.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.