Title : A Cell-Permeant Mimetic of NMN Activates SARM1 to Produce Cyclic ADP-Ribose and Induce Non-apoptotic Cell Death.

Pub. Date : 2019 May 31

PMID : 31128467






4 Functional Relationships(s)
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Compound Name
Protein Name
Organism
1 SARM1, an NAD-utilizing enzyme, regulates axonal degeneration. NAD sterile alpha and TIR motif containing 1 Homo sapiens
2 We show that CZ-48, a cell-permeant mimetic of NMN, activated SARM1 in vitro and in cellulo to cyclize NAD and produce a Ca2+ messenger, cADPR, with similar efficiency as NMN. NAD sterile alpha and TIR motif containing 1 Homo sapiens
3 Both catalyzed similar set of reactions, but SARM1 had much higher NAD-cyclizing activity, making it more efficient in elevating cADPR. NAD sterile alpha and TIR motif containing 1 Homo sapiens
4 In SARM1-overexpressing cells, CZ-48 elevated cADPR, depleted NAD and ATP, and induced non-apoptotic death. NAD sterile alpha and TIR motif containing 1 Homo sapiens