Caffeine and 23 other compounds protect against harmful proteins associated with dementia, by boosting the activity of an enzyme in the brain, says a new study published in Scientific Reports.
A group of 24 compounds, including caffeine, have been found to boost a brain enzyme that is thought to provide protection against dementia. These results will hopefully assist scientists to engineer drugs targeting the enzyme to guard against the adverse effects of neurodegenerative conditions, says lead author, Hui-Chen Lu, from Indiana University (IU).
The enzyme, named NMNAT2, was identified last year. Lu and her colleagues had also discovered its dual-role:
- A protective function
It shields neurones from stress.
- A chaperone function
It gets rid of mis-folded proteins (named tau) which tend to build up in areas of the brain, creating plaques—a phenomenon associated with ageing, and linked with neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS (amyotrophic lateral sclerosis).
As a next step, Lu and his team, then, decided to test the effects of over 1,280 compounds on NMNAT2, with the aim of finding one that would exert some positive influence on the synthesis of the enzyme; the reasoning was that more of this enzyme would lead to fewer mis-folded proteins associated with dementia and similar disorders. Their results show that 24 of these substances can enhance its production. Caffeine, one of the said compounds, was also found to boost memory.
When the IU team wanted to confirm the benefits of caffeine by administering it to mice engineered to produce lower concentrations of NMNAT2, they found that the mice began producing normal levels of the enzyme.
Other compounds with the observed benefits include rolipram (which used to be considered an antidepressant), ziprasidone, cantharidin, wortmannin, and retinoic acid.
On the other hand, another set of compounds (13 of them) were found to have the opposite effect: they appeared to reduce the production of the enzyme. Lu explains that a better understanding of their roles will also provide invaluable information into how they lead to dementia.