Researchers at Indiana University have found 24 compounds that can boost an enzyme in the brain that may protect against dementia.
The enzyme, called NMNAT2, was discovered by a team of researchers at IU Bloomington in 2016.
NMNAT2 serves a protective function in the brain by protecting neurons from stress and a “chaperone function” to combat misfolded proteins known as tau. Lu Tau accumulates in the brain as plaques and has been linked to neurodegenerative disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases along with amyotrophic lateral sclerosis or ALS.
“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, a professor in the Department of Psychological and Brain Sciences at IU Bloomington’s College of Arts and Sciences, said in a press release.
Researchers screened more than 1,280 compounds to find ones with the potential to impact the production of NMNAT2, identifying 24 compounds with the potential to increase the production.
The research revealed caffeine was one of the substances that increases production of NMNAT2. Caffeine also appears to improve memory function in mice genetically modified to produce high levels of misfolded tau proteins, which contribute to the development of dementia.
Researchers also found that mice modified to produce misfolded tau made lower levels of NMNAT2.
Other proteins that boosted NMNAT2 production include rolipram, ziprasidone, cantharidin, wortmannin and retinoic acid.
“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,” Lu said.
The study was published in Scientific Reports.