SARM1
SARM1 (sterile alpha and TIR motif containing 1, also known as SARM, SAMD2 or KIAA0524) is an NAD(+) hydrolase that drives axonal degeneration after injury by regulating NAD(+) metabolism. It also acts in innate immune signalling and programmed cell death. Browse Assay Genie's current range of SARM1 research reagents below, or read on for the biology behind the target.
SARM1 is an NAD(+) hydrolase that plays a key role in axonal degeneration following injury. In response to injury, SARM1 is activated and catalyses cleavage of NAD(+) into ADP-D-ribose (ADPR), cyclic ADPR (cADPR) and nicotinamide. The resulting NAD(+) depletion promotes cytoskeletal degradation and axon destruction, the hallmark of Wallerian degeneration, an injury-induced form of programmed subcellular death in which the axon distal to the injury site degenerates. SARM1 can also hydrolyse NADP(+), but not other NAD(+)-related molecules, and it can activate neuronal cell death in response to stress.
Beyond axon injury, SARM1 regulates dendritic arborisation through the MAPK4-JNK pathway. It is also involved in innate immune responses, where it acts as a negative regulator of MYD88- and TRIF-dependent toll-like receptor signalling. It inhibits TICAM1/TRIF- and MYD88-dependent activation of JUN/AP-1, TRIF-dependent activation of NF-kappa-B and IRF3, and phosphorylation of MAPK14/p38. SARM1 has also been described as a sequence-independent sensor of non-self double-stranded DNA, which elicits NAD(+) degradation and promotes programmed cell death. NCBI Gene annotation lists double-stranded DNA binding, hydrolase activity on N-glycosyl compounds and identical protein binding.
The SARM1 protein is located in the cytoplasm, including axons, dendrites and synapses, and is active in the mitochondrion. HGNC places the SARM1 gene in the sterile alpha motif domain containing, TIR domain containing and armadillo like helical domain containing groups, and UniProt assigns it to the SARM1 family. Orthologous genes are present in mouse and rat, both named Sarm1.
SARM1 hydrolyses NAD(+) after injury, promoting cytoskeletal degradation and axon destruction in Wallerian degeneration.
SARM1 cleaves NAD(+) into ADPR, cADPR and nicotinamide, and also hydrolyses NADP(+), making it a focus for NAD(+) turnover studies.
SARM1 negatively regulates MYD88- and TRIF-dependent toll-like receptor signalling, including AP-1, NF-kappa-B, IRF3 and p38 activation.
SARM1 can activate neuronal cell death in response to stress and acts as a dsDNA sensor promoting programmed cell death.
SARM1 is an NAD(+) hydrolase. After injury it is activated and cleaves NAD(+) into ADPR, cADPR and nicotinamide. This NAD(+) depletion promotes cytoskeletal degradation and axon destruction, driving Wallerian degeneration. It also regulates dendritic arborisation and negatively regulates toll-like receptor signalling.
SARM1 stands for sterile alpha and TIR motif containing 1. Aliases include SARM, SAMD2 and KIAA0524, and UniProt names the protein NAD(+) hydrolase SARM1. Its enzyme classification is EC 3.2.2.6. Check the datasheet of any product for its validated reactivity.
Yes. Mouse and rat each have an orthologous gene named Sarm1. The protein belongs to the SARM1 family, and its sterile alpha motif, TIR and armadillo-like helical domains are reflected in the HGNC gene groups. Check the datasheet of any product for its validated reactivity.
Toll-like receptor adaptors, MAPK pathway components and transcription factors linked to SARM1 signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q6SZW1; product specifications from Assay Genie datasheets.