Subsequent projects

Prof. Dr. Michael Decker
University of Würzburg
Pharmaceutical/Medicinal Chemestry

Dr. Pamela Maher
The Salk Institute for Biol. Stud, SNL-D
Cellular Neurobiology Laboratory

Development of molecular probes based on cannabinol (CBN) for target fishing via activity-based protein profiling to identify intracellular targets for neuroprotectivity

Recently, we and others have described several natural products as potent neuroprotectants, i.e., compounds that prevent the death of neurons. Such compounds are even able to drastically revert cognitive decline in animal models of neurodegeneration, e.g., Alzheimer’s disease. Such compounds have largely unknown molecular targets in the cells, therefore - at the current stage - chemical improvement is difficult, if not impossible.

Our labs successfully applies a “target-fishing” approach, e.g., to flavonoids. This appoach uses activity-based protein profiling to identify intracellular targets. We now want to apply this approach also to a recently described class of “druggable” neuroprotectants belonging to the class of phytocannabinoids. Cannabinol (CBN) represents such a phytocannabinoids that is not targeting cannabinoid (CB1/CB2) receptors. This is a remarkable feature, especially since activity at the CB1 receptor is responsible psychotropic effects, which need to be avoided for neuroprotectants. CBN can instead modulate several key biological pathways in mitochondria (oxytosis/ferroptosis) and thereby causes neuroprotection.

To identify intracellular targets of natural products, we will design, develop and synthesize a suitable chemical probes, e.g., based on CBN, which can be photoactivated. If the chemical probes acts like CBN (and does not bind to cannabinoid receptors), target evaluation will be performed using both confocal fluorescence microscopy (for localisation studies) and affinity pulldown of proteins with subsequent mass spectrometric-analysis to identify the yet unknown molecular targets of phytocannabinoids and other natural products in the cell.


Primary project: Discovery and development of natural product-based neuroprotective compounds and elucidation of their molecular mode of action


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