A study, led by researchers including Yousuf O. Ali, Gillian Bradley and Hui-Chen Lu?from Indiana University (IU) and funded by the National Institutes of Health and the Belfer Family Foundation, have identified molecules that can help prevent neurodegeneration. The molecules might provide an effective therapeutic intervention to reserve cognitive function in neurodegenerative diseases. The new study, published in Scientific Reports, has identified 24 molecules that could increase the production of an enzyme called NMNAT2 in the brain of mouse models. This enzyme is known to play a role in maintaining neuronal health, and enhancing its function is believed to be a therapeutic strategy to reserve cognitive function in neurodegenerative diseases. Neurodegenerative diseases are some of the most debilitating disorders that result in progressive degeneration and/or death of nerve cells. This causes problems with movement, thinking, feelings, cognition, and memory. Examples of neurodegenerative diseases include Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, Prion disease, Spinocerebellar ataxia, and Spinal muscular atrophy. A key molecular pathway involved in many different neurodegenerative diseases is the misfolding and buildup of proteins in the brain. A growing body of evidence suggests that accumulation of misfolded proteins contributes to synaptic dysfunction, neuronal apoptosis, brain damage, and disease. Tau is one such protein. Tau protein may become defective, no longer function properly, and form plaques in the brain, which is implicated in Alzheimer's disease, Parkinson's disease, and other tauopathies. In previous research, IU scientists uncovered that the enzyme NMNAT2 not only guards neurons from stress but also helps combat misfolded tau proteins. Additionally, NMNAT2 levels in Alzheimer’s disease brains are much lower than in control brains. For the current study, IU scientists made efforts to find molecules that can modulate NMNAT2 levels in the brain. Using a newly developed method called NMNAT2-MSD-based assay, they screened 1280 pharmacologically active molecules and identified 37 NMNAT2 modulators: 24 compounds that boost the production of NMNAT2 and 13 compounds that decrease the production of NMNAT2. One of the compounds that boost NMNAT2 production was caffeine. Treatment of caffeine restored NMNAT2 expression to control levels in mice modified to produce lower levels of NMNAT2. IU scientists also found that some compounds regulated neuronal viability in an NMNAT2-specific manner. “We believe the knowledge of these pathways may promote better translational approaches for targeting NMNAT2 in various neurodegenerative diseases,“ said the researchers. Cusabio provides NMNAT2, and Recombinant FGFR4.