Zeroing In on Coffee’s Potential Use Against Neurodegenerative Disease

By Josh Garcia
Wednesday, May 1, 2019
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The health effects of coffee are not a novel field of research. A study in Comprehensive Reviews in Food Science and Food Safety in 2016 determined that the benefits of moderate coffee consumption among adults clearly outweigh its risks, and numerous studies have evaluated its possible neuroprotective effects.

However, scientists are now placing additional focus on the mechanism behind those potential benefits. Canadian researchers recently discovered that phenylindanes in coffee inhibit the aggregation of both amyloid-beta and tau proteins, which contribute to the development of Parkinson’s and Alzheimer’s diseases.

The researchers examined how compounds in coffee affect proteins associated with neurodegenerative disease. The proteins they examined, while harmless as single proteins, become toxic to brain cells once they aggregate and clump together.

“We began with instant coffee extracts, which we dosed into acid to see if they had any effect on aggregation,” says Ross Mancini, PhD, Post-Doctoral Research Fellow in Medicinal Chemistry at the Department of Fundamental Neurobiology, Krembil Research Institute at the University of Toronto. “After the simple panel came back positive, we wanted to point to a specific component or mixture of components as being responsible for this effect.”

Mancini and his colleagues noticed that darker roasts, whether caffeinated or decaffeinated, did a better job inhibiting the aggregation of amyloid-beta and tau proteins than their lighter counterparts. Further research showed darker roasts had a higher concentration of phenylindanes than lighter roasts. As such, when the researchers decided to directly examine some of the compounds found in coffee, phenylindanes were on the list. Compounds tested also included caffeine, chlorogenic acid, quinic acid, caffeic acid and quercetin.

“Even if they are found to not cross the blood-brain barrier, phenylindanes are an interesting starting point in developing new compounds [with similar effects on amyloid-beta and tau proteins] that are more drug-like and can cross the blood-brain barrier.”
— Donald Weaver, MD, PhD, Director of the Krembil Research Institute at the University of Toronto

Promising Phenylindanes

The separate compounds were examined in a test tube as opposed to a human or animal model. Though compounds including chlorogenic acid, caffeic acid and quercetin inhibited amyloid-beta aggregation, only phenylindanes inhibited the aggregation of both amyloid-beta and tau proteins.

“We can’t immediately say that these are the reasons why coffee has a neuroprotective effect on the brain,” says Donald Weaver, MD, PhD, Director of the Krembil Research Institute. “The brain is protected by the blood-brain barrier, and we don’t know if these compounds have the ability to cross it.”

However, researchers believe the study may serve as a foundation for possible development of interventions to treat or prevent neurodegenerative diseases in the future.

“A pharmacokinetic study to determine if phenylindanes can get into the brain will help us determine if these compounds will be useful from a drug standpoint,” Mancini says. “Once that data is retrieved, it will give us a chance to re-evaluate and see where to go next.”

If phenylindanes do cross the blood-brain barrier, further research can be performed to determine how to modify them to be more useful in a medicinal context or create similar compounds that could be valuable in developing drug therapies.

“Mother Nature is a bloody good chemist,” Dr. Weaver says. “It’s good to look at natural products as the starting point of future therapeutic agents because they play an important role in the history of drug discovery. For example, penicillin is a natural product.”

As of now, the study does not provide enough evidence to encourage coffee drinkers to switch to dark roasts, according to researchers.

“All we’re saying is that phenylindanes show this attractive activity, and there are more of them in dark-roast coffee,” Mancini says. “It’s just another potential piece in a complex puzzle.”