REVIEW article

Front. Immunol.

Sec. Inflammation

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1521364

This article is part of the Research TopicCommunity Series in Pathogenetic mechanism and therapeutic target for inflammation in autoimmune disease: Volume IIView all 9 articles

SARM1: a key multifaceted component in immunoregulation, inflammation and neurodegeneration

Provisionally accepted
Samuel dos Santos OliveiraSamuel dos Santos Oliveira1João Vinícius SilvaJoão Vinícius Silva2Raquel VieiraRaquel Vieira2Luís Felipe SerraLuís Felipe Serra2Pedro Henrique BandeiraPedro Henrique Bandeira2Beatriz LeocataBeatriz Leocata2Marco AtaídeMarco Ataíde3Niels Olsen Saraiva CamaraNiels Olsen Saraiva Camara2*
  • 1University of São Paulo, Ribeirão Preto, Ribeirão Preto, Brazil
  • 2University of São Paulo, São Paulo, Rio Grande do Sul, Brazil
  • 3Amgen Inc - SSF, South San Francisco, California, United States

The final, formatted version of the article will be published soon.

Select one of your emails

You have multiple emails registered with Frontiers:

Notify me on publication

Please enter your email address:

If you already have an account, please login

You don't have a Frontiers account ? You can register here

The downstream signaling pathways of TLR activation involve a family of adaptor proteins, including MYD88, TIRAP, TRIF, TRAM, and SARM1. The first four proteins stimulate inflammatory and antiviral responses, playing crucial roles in innate immunity against various pathogens. In contrast, SARM1 promotes immunity to microorganisms in invertebrate animals independently of TLRs, and negatively regulates inflammatory responses in metazoan organisms. SARM1 inhibits TRIF, reduces the activation of various inflammasomes, and induces mitochondrial damage and cell death to eliminate hyperactivated cells. This regulation is essential to ensure timely control of immune responses and to prevent excessive inflammation. Recently, it was discovered that SARM1 can hydrolyze NAD, a critical component of cellular metabolism. The reduction of NAD levels by SARM1 is linked to the progression of Wallerian degeneration following neuronal injury and may also play a role in the immunoregulation of lymphoid and myeloid cells. Since SARM1 can be pharmacologically modulated, it presents promising opportunities for developing treatments for inflammatory and neurodegenerative diseases.

Keywords: innate immunity3, immunometabolism4, cell death5, Immunoregulation, neurodegenerative disease

Received: 01 Nov 2024; Accepted: 22 Apr 2025.

Copyright: © 2025 Oliveira, Silva, Vieira, Serra, Bandeira, Leocata, Ataíde and Camara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Niels Olsen Saraiva Camara, University of São Paulo, São Paulo, Rio Grande do Sul, Brazil

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material