A new study suggests that there may be more uses for caffeine than simply providing a morning fix. It has the potential to protect against dementia and other neurodegenerative disorders.
Using a novel high-throughput screening platform, the researchers tested more than 1,280 pharmacologically active compounds to see how they affected NMNAT2 production in brain cells.
Lu and colleagues found that mice that had been genetically modified to produce misfolded tau proteins had low NMNAT2 production.
In this study, the team administered caffeine to mice that had been genetically modified to produce low NMNAT2 levels. The researchers found that the rodents began producing the enzyme at levels comparable to those of normal mice.
Rolipram – a compound that was used as an antidepressant in the 1990s but that was later discontinued – was also identified as a highly promising candidate for boosting NMNAT2 production.
Other studies have also shown that rolipram can break down misfolded tau proteins.
Other compounds that showed potential for increasing NMNAT2 production included ziprasidone, cantharidin, wortmannin, and retinoic acid, though these were not as effective as caffeine and rolipram.
Additionally, the researchers identified 13 compounds that reduce NMNAT2 production. Lu says that uncovering these compounds is important, as they may play a role in the development of dementia and other neurodegenerative conditions.
While further research is needed to determine which compounds are best for increasing NMNAT2 production, this current study has certainly made a strong start. The team believes that the findings could aid the development of new drugs for the prevention of Alzheimer’s and other neurodegenerative diseases involving misfolded proteins, such as Parkinson’s disease and Lou Gehrig’s disease.
Hui-Chen Lu said that “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.”
