The sterile alpha and TIR motif-containing protein 1 (SARM1) belongs to the family of Toll/interleukin-1 receptor (TIR)-domain-containing proteins¹. This protein is characterized by its multidomain structure, including N-terminal Armadillo repeats (ARM), tandem sterile alpha motif (SAM) domains, and a C-terminal catalytic TIR domain². SARM1 is an intracellular protein predominantly localized in the axons of neurons. It plays a critical role in axonal self-destruction through its NAD⁺ glycohydrolase activity, which is initiated under pathological conditions such as axonal injury^2,3.

SARM1 expression is prominent in neuronal populations, particularly within the central and peripheral nervous systems. It is upregulated under stress conditions, such as hypoxia and neuroinflammatory states³. The activation of SARM1 is regulated by nicotinamide mononucleotide (NMN), which disrupts the interaction between the ARM and TIR domains, leading to the formation of TIR-domain assemblies that execute NAD⁺ cleavage^2,4.

Biologically, SARM1 is implicated in Wallerian degeneration, a process of axonal degeneration triggered by trauma or neuropathies. It also mediates axonal degeneration in metabolic and toxic neuropathies, such as those induced by high-fat diets or chemotherapy agents like paclitaxel^3,5. In vitro studies have shown that genetic deletion of SARM1 protects neurons from degeneration by maintaining NAD⁺ levels. Similarly, in vivo studies reveal its role in preserving axonal integrity in models of traumatic, toxic, and metabolic insults^3,5. Dysregulation of SARM1 activity is associated with various neurodegenerative conditions, including peripheral neuropathies, glaucoma, and traumatic brain injuries^2,3.