Novel Biosensor for Direct Measurement of Bioavailable NAD+
OHSU # 1988
This technology provides a unique cell-based platform for targeting NAD+-(nicotinamide adenine dinucleotide) regulatory pathways in the treatment of human diseases. An emerging theme in age-related pathologies—e.g. neurodegeneration, cancer, cardiovascular disease, inflammation, type 2 diabetes, and metabolic disease—is due to the misregulation of NAD+ metabolism and homeostasis.
NAD+ serves dual roles as both an intermediary metabolite and as a required co-substrate for Sirtuin and PARP enzymes, and thus is positioned centrally in a number of biological processes. However, techniques to dynamically monitor free NAD+ in live cells or specific subcellular organelles has eluded the research community. This has had tremendous impact on the development of novel therapies. NAD+ exists in distinct intracellular pools, each compartmentalized and whose concentrations are under local control. To overcome this limitation, researchers at Oregon Health & Science University developed a genetically-encoded fluorescent biosensor for direct measurement of the bioavailable NAD+ levels in specific cellular compartments.
Figure. NAD+ binding causes a loss of fluorescence from the sensor. (top) depiction of cpVenus (cpV) and the bipartite NAD+ binding domain (blue). (bottom) Fluorescence emission and excitation scans at indicated NAD+ concentrations. Inset shows fluorescence from excitation at 405nm.
- Richard Goodman, VI.Vollum Institute
- Michael Cohen, SM.Physiology & Pharmacology
- Xiaolu (Lulu) Cambronne, VI.Vollum Institute
- Melissa Stewart, VI.Vollum Institute
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