SARM1 Antibodies

Background

SARM1 is a protein located within cells and is mainly expressed in the axons of neurons. This protein exists in a self-inhibitory form under normal conditions. When nerve damage or metabolic stress leads to a decrease in NAD+ levels, its inherent NAD+ hydrolase activity will be activated, thereby triggering the axonal degeneration program. Due to its core role in mediating mitochondrial dysfunction and axonal degeneration, SARM1 has become a key target in the research of neurodegenerative diseases. In 2017, multiple studies jointly clarified its molecular mechanism as an NAD+ consuming enzyme. This discovery has promoted the development of neuroprotective strategies for diseases such as Alzheimer's disease and Parkinson's disease. Its functional positioning as a programmed axonal executor provides an important molecular basis for understanding the injury response and self-defense mechanisms of the nervous system.

Structure Function Application Advantage Our Products

Structure of SARM1

SARM1 is a protein composed of approximately 900 amino acids with a molecular weight of about 100 kDa. As the core executor of axonal mutability, its structure consists of an N-terminal self-suppression domain, a TIR domain, and a unique SAM domain. The SARM1 sequences among different species are highly conserved, especially within the catalytic TIR domain.

Species	Human	Mouse	Rat	Zebrafish
Molecular Weight (kDa)	About 100	About 100	About 100	About 105
Primary Structural Differences	Typical mammalian SARM1 structure, containing the complete autoinhibitory module	Highly homologous to humans, it is the main animal model	Structure similar to mice	Retain the core TIR domain for neural regeneration research

The core functional domain of this protein is the TIR domain capable of hydrolyzing NAD+. Under normal circumstances, its N-terminal and SAM domains will form self-inhibition, preventing the activity of TIR. When axon injury or energy stress leads to a decrease in NAD+ levels, this inhibitory effect is lifted, and the activated TIR domain will rapidly consume NAD+ within the cell, thereby actively triggering programmed axonal degeneration. This mechanism plays a key role in various neurodegenerative diseases.

Fig. 1 Schematic representation of protein domains and motifs found in SARM1.¹

Key structural properties of SARM1:

Multi-domain self-suppression structure: It includes ARM, SAM and TIR domains
NAD+ hydrolysis active center: Located within the TIR domain
Allosteric regulation mechanism: remove axonal injury signal suppression, activate the enzyme activity

Functions of SARM1

The core function of the SARM1 gene is to perform programmed axonal degeneration, which is an active clearance mechanism after nerve injury. At the same time, it is also involved in the immune regulation and metabolic stress response of the nervous system.

Function	Description
Axonal degeneration is performed in the core	When nerve injury or lesion occurs, its TIR domain is activated, actively triggering the self-degradation of axons by rapidly consuming NAD+ within the axons.
Neuroimmune regulation	Involved in regulating nerve inflammation, its activation associated molecular patterns of damage can be released, affect the function of microglial cells and other immune cells.
Metabolic stress sensor	As a key sensor of neuronal energy status (especially NAD+ levels), it initiates protective or destructive pathways when metabolic imbalance occurs.
Common pathways of neurodegenerative diseases	In various disease models such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, its activation has been confirmed to be a key downstream event of axonal injury.
Potential neuroprotective targets	Inhibiting its NAD+ hydrolytic activity has been proven to effectively delay or prevent axonal degeneration in various animal models and has therapeutic potential.

The activation of SARM1 has a "all or none" switching characteristic, and its NAD+ hydrolysis activity shows sharp positive feedback above the threshold, which contrasts sharply with the gentle oxygen-binding curve of myoglobin, reflecting its role as a decisive executive molecule in injury response.

Applications of SARM1 and SARM1 Antibody in Literature

Liu, Huitao, et al. "SARM1 promotes neuroinflammation and inhibits neural regeneration after spinal cord injury through NF-κB signaling." Theranostics 11.9 (2021): 4187. https://doi.org/10.7150/thno.49054

The article indicates that after spinal cord injury, SARM1 is upregulated in neurons and astrocytes, mediating axonal degeneration and neuroinflammation. Inhibiting the NF-κB pathway and upregulating HSP70 can promote nerve regeneration and functional recovery. Targeting SARM1 is a potential therapeutic strategy.

Miao, Xuemeng, et al. "SARM1 promotes neurodegeneration and memory impairment in mouse models of Alzheimer's disease." Aging and disease 15.1 (2024): 390. https://doi.org/10.14336/AD.2023.0516-1

The article indicates that in Alzheimer's disease, conditional knockout of SARM1 in the central nervous system can delay cognitive decline, reduce beta-amyloid protein deposition and inflammatory infiltration, and the mechanism may be related to the down-regulation of the TNF-α signaling pathway.

Oliveira, Samuel dos Santos, et al. "SARM1: a key multifaceted component in immunoregulation, inflammation and neurodegeneration." Frontiers in Immunology 16 (2025): 1521364. https://doi.org/10.3389/fimmu.2025.1521364

The article indicates that SARM1 plays a unique role in the TLR pathway. It inhibits inflammatory signals, mediates mitochondrial damage and cell death by degrading NAD+ to regulate the immune system and prevent overreactions, making it a potential target for treating neurodegenerative and inflammatory diseases.

Wang, Lina, et al. "SARM1 senses dsDNA to promote NAD+ degradation and cell death." Cell (2025). https://doi.org/10.1016/j.cell.2025.09.026

The article indicates that the DNA perception mechanism remains unclear. SARM1 is a key axonic executive protein with NADase activity. Its unique octamer cyclic activated state structure suggests that linear molecules such as double-stranded DNA may directly activate SARM1, providing a new perspective for understanding the related disease mechanisms.

McGuinness, Helen Y., et al. "SARM1-Dependent axon degeneration: nucleotide signaling, neurodegenerative disorders, toxicity, and therapeutic opportunities." The Neuroscientist 30.4 (2024): 473-492. https://doi.org/10.1177/10738584231162508

The article indicates that SARM1 is a key NAD+ hydrolase mediating axonal degeneration, and its activation is regulated by the NMN/NAD+ ratio, playing a core role in various neurodegenerative diseases. A thorough understanding of its structure and regulatory mechanism provides a new target for the development of axonal protection therapy.

Creative Biolabs: SARM1 Antibodies for Research

Creative Biolabs specializes in the production of high-quality SARM1 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom SARM1 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our SARM1 antibodies, custom preparations, or technical support, contact us at email.

Reference

McGuinness, Helen Y., et al. "SARM1-Dependent axon degeneration: nucleotide signaling, neurodegenerative disorders, toxicity, and therapeutic opportunities." The Neuroscientist 30.4 (2024): 473-492. https://doi.org/10.1177/10738584231162508