Recombinant Human SARM1 protein

SARM1 (Sterile Alpha and TIR Motif-Containing Protein 1) is a NADase enzyme that plays a central role in axonal degeneration, a process linked to neurodegenerative disorders and nerve injury. Initially identified as a member of the MyD88-like TIR-domain protein family involved in innate immunity, SARM1 was later found to act as a key executioner of axonal self-destruction. Unlike other TLR adaptors, SARM1’s primary function in neurons revolves around its ability to deplete NAD+ (nicotinamide adenine dinucleotide), a critical metabolic cofactor, through its intrinsic enzymatic activity. Under normal conditions, SARM1 remains autoinhibited, but cellular stress signals (e.g., injury, metabolic imbalance) trigger its activation, initiating a local NAD+ depletion cascade that disrupts energy homeostasis and culminates in axonal fragmentation.

Recombinant SARM1 protein, typically produced in bacterial or insect cell expression systems, has become a vital tool for studying its structure, enzymatic mechanisms, and regulatory interactions. Researchers use purified SARM1 to characterize its TIR (Toll/interleukin-1 receptor) domain-driven NADase activity, map binding partners, and screen for inhibitors. Structural studies of recombinant SARM1 have revealed its multi-domain architecture, including ARM (Axon Degeneration Sterile Motif) and SAM (Sterile Alpha Motif) domains that regulate oligomerization and activation. Notably, the autoinhibitory mechanism and activation triggers (e.g., NMN accumulation, loss of NAD+) have been elucidated using recombinant systems. Such work informs therapeutic strategies targeting SARM1 to treat neurodegenerative diseases (e.g., ALS, glaucoma) or traumatic nerve injuries by blocking its NADase activity. Current challenges include understanding context-dependent regulatory switches and optimizing drug candidates that modulate SARM1 without disrupting its potential physiological roles in immunity or homeostasis.