Researchers from Indiana University found that caffeine and 23 other compounds can boost the production of an enzyme called nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2), which may block processes associated with dementia development.
Worldwide, there are around 47.5 million people living with dementia. By 2050, this number is expected to more than triple.
Alzheimer’s disease is the most common form of dementia, accounting for around 60-80 percent of all cases. The disease is characterized by problems with thinking and memory, as well as confusion, disorientation, and changes in mood and behavior.
Though researchers are still unclear on the precise causes of Alzheimer’s, it is known that the condition arises as a result of brain cell death. The formation of “tangles,” which are misfolded strands of a protein called tau, is believed to play a role in brain cell death.
For the new study, Lu and colleagues sought to identify compounds that can increase the production of NMNAT2 and boost its protective effects.
Caffeine increased NMNAT2 production in mice
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.
The team identified 24 compounds that showed potential for increasing NMNAT2 production, with caffeine standing out as the most promising candidate.
Past research has shown caffeine to boost memory in mice with misfolded tau proteins, and in their previous study, 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.
Findings may fuel drug development
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.
“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.”
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