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Updated: Jul 4, 2026

Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
08:37

Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity

Published on: October 25, 2016

OTUB1 non-canonically inhibits TAB2 ubiquitination to govern microglia-mediated neuroinflammation

Zijun Cao1,2, Zhenhu Zhu2, Ping Zeng1,2

  • 1School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.

EMBO Molecular Medicine
|July 2, 2026
PubMed

Insights

The deubiquitinating enzyme OTUB1 drives neuroinflammation by enhancing Toll-like receptor signaling in microglia. Inhibiting OTUB1 reduces brain injury and neuroinflammation, offering a potential therapeutic target for CNS diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Molecular Biology

Background:

  • Microglia are key players in central nervous system (CNS) neuroinflammation, contributing to disease pathogenesis.
  • Dysregulated microglial activation exacerbates CNS diseases.

Purpose of the Study:

  • To investigate the role of the deubiquitinating enzyme OTUB1 in microglial activation and CNS inflammation.
  • To explore OTUB1 as a potential therapeutic target for neuroinflammatory diseases.

Main Methods:

  • Microglia-specific OTUB1 deletion in mice.
  • Assessment of ischemic brain injury, lipopolysaccharide-induced sickness behavior, and experimental autoimmune encephalomyelitis.
  • Analysis of Toll-like receptor (TLR) signaling pathways and cytokine induction.
  • Pharmacological inhibition of OTUB1.

Main Results:

  • Microglia-specific OTUB1 deletion ameliorated ischemic brain injury by reducing microglial pro-inflammatory activation.
  • OTUB1 enhances TLR signaling by stabilizing UBC13 and TAB2, independent of its catalytic activity, by reducing TAB2 proteasomal degradation.
  • OTUB1 deficiency in microglia alleviated sickness behavior and experimental autoimmune encephalomyelitis.
  • Pharmacological OTUB1 inhibition mitigated ischemic stroke injury in mice.

Conclusions:

  • OTUB1 is a critical regulator of microglial activation and neuroinflammation.
  • Targeting OTUB1 presents a promising therapeutic strategy for TLR-associated neuroinflammatory diseases.

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