Caffeine may keep cognitive decline and dementia at bay by boosting the levels of a protective protein called NMNAT2, a new study concludes.
The study, “Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons,” appeared in the journal Scientific Reports.
NMNAT2 plays a key role in neuronal function, protecting neurons against several diseases by working as a “chaperone” — a type of protein that ensure other proteins are properly produced. However, in ALS, Alzheimer’s, Huntington’s and Parkinson’s diseases – all of which are characterized by the accumulation of faulty proteins – NMNAT2 levels are significantly reduced. So increasing the levels of this protein could potentially boost neuronal function and protect against dementia.
Using a technique developed in their lab, researchers at Indiana University screened 1,280 compounds, including existing drugs, looking for molecules that could either raise or lower NMNAT2 levels. They identified 24 such compounds; caffeine was among molecules that increased NMNAT2 levels. Indeed, when researchers fed caffeine to mice with high levels of faulty tau (one of the proteins involved in Alzheimer’s), their NMNAT2 levels went back to normal and memory function improved.
“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,” Hui-Chen Lu, the study’s senior author, said in a news release.
Other molecules were shown to promote NMNAT2 production in the brain, such as ziprasidone, cantharidin, wortmannin and retinoic acid (derived from vitamin A), although their effect was not as strong as that of caffeine, according to the study, which was funded by the National Institute of Neurological Disorders and Stroke (a unit of the National Institutes of Health) and the Belfer Family Foundation.
Researchers also identified 13 molecules that reduce NMNAT2 expression, but more studies are necessary to understand their role in the body and their contribution to dementia.
“While increasing NMNAT2 abundance in neurodegenerative conditions may provide therapeutic benefit, it is equally if not more important to understand why NMNAT2 levels are reduced in various neurodegenerative conditions,” researchers wrote. “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.”