Rubicon modulates neuroimmune responses following traumatic brain injury.
4 affiliations
- 1Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD, USA.
- 2Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD, USA.
- 3Department of Anesthesiology and Shock, Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, MD, USA. [email protected].
- 4Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA. [email protected].
Abstract
Traumatic brain injury (TBI) elicits robust neuroinflammation and oxidative stress, coupled with an acute inhibition of macro-autophagy (autophagy) in neurons and microglia. Rubicon (Rubcn), a Beclin1 interacting protein that suppresses autophagy and mediates LC3-associated phagocytosis and endocytosis (LAP/LANDO), influences inflammatory signaling in metabolic, neurodegenerative, and inflammaging diseases; yet its role in acquired brain injury has not been examined. Using a controlled cortical impact model, we investigated the role of Rubicon in acute neuroinflammatory responses following injury by comparing wild-type and Rubcn-mutant mice. Bulk-RNA sequencing of injured cortex revealed attenuated induction of inflammatory pathways and reduced activation of pro-inflammatory microglial/macrophage phenotype in injured Rubcn-mutant mice. Rubcn-mutant mice demonstrated less pronounced inhibition of autophagy during the acute phase of injury. Although the inflammatory differences were transient, Rubicon mutant mice exhibited improved motor coordination and gait stability during recovery. Proteomic analyses revealed the presence of a truncated Rubicon protein in the mutant mice and identified the negative regulator of reactive oxygen species (NRROS) as a novel interactor of Rubicon. Consistent with this interaction, Rubcn-mutant mice displayed markedly reduced oxidative damage, indicated by decreased lipid peroxidation after injury. Together, these findings indicate that Rubicon promotes acute neuroinflammatory and oxidative stress responses following TBI by modulating autophagy and ROS production. Rubicon-mediated pathways may serve as therapeutic targets to attenuate inflammation-mediated damage after TBI.
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BibTeX
@article{thapa2026rubicon,
title = {{Rubicon modulates neuroimmune responses following traumatic brain injury.}},
author = {Sagarina Thapa and Amir Mehrabani-Tabari and Olivia Pettyjohn-Robin and Dexter Ph Nguyen and Mehari M Weldemariam and Chinmoy Sarkar and Maryam Khan and Maureen A Kane and Marta M Lipinski},
journal = {Cell death \& disease},
year = {2026},
month = jul,
doi = {10.1038/s41419-026-09083-4},
url = {https://europepmc.org/article/MED/42907430},
note = {CC BY},
}
RIS
TY - JOUR
TI - Rubicon modulates neuroimmune responses following traumatic brain injury.
AU - Sagarina Thapa
AU - Amir Mehrabani-Tabari
AU - Olivia Pettyjohn-Robin
AU - Dexter Ph Nguyen
AU - Mehari M Weldemariam
AU - Chinmoy Sarkar
AU - Maryam Khan
AU - Maureen A Kane
AU - Marta M Lipinski
PY - 2026
DA - 2026/07/01
JO - Cell death & disease
DO - 10.1038/s41419-026-09083-4
UR - https://europepmc.org/article/MED/42907430
AB - Traumatic brain injury (TBI) elicits robust neuroinflammation and oxidative stress, coupled with an acute inhibition of macro-autophagy (autophagy) in neurons and microglia. Rubicon (Rubcn), a Beclin1 interacting protein that suppresses autophagy and mediates LC3-associated phagocytosis and endocytosis (LAP/LANDO), influences inflammatory signaling in metabolic, neurodegenerative, and inflammaging diseases; yet its role in acquired brain injury has not been examined. Using a controlled cortical impact model, we investigated the role of Rubicon in acute neuroinflammatory responses following injury by comparing wild-type and Rubcn-mutant mice. Bulk-RNA sequencing of injured cortex revealed attenuated induction of inflammatory pathways and reduced activation of pro-inflammatory microglial/macrophage phenotype in injured Rubcn-mutant mice. Rubcn-mutant mice demonstrated less pronounced inhibition of autophagy during the acute phase of injury. Although the inflammatory differences were transient, Rubicon mutant mice exhibited improved motor coordination and gait stability during recovery. Proteomic analyses revealed the presence of a truncated Rubicon protein in the mutant mice and identified the negative regulator of reactive oxygen species (NRROS) as a novel interactor of Rubicon. Consistent with this interaction, Rubcn-mutant mice displayed markedly reduced oxidative damage, indicated by decreased lipid peroxidation after injury. Together, these findings indicate that Rubicon promotes acute neuroinflammatory and oxidative stress responses following TBI by modulating autophagy and ROS production. Rubicon-mediated pathways may serve as therapeutic targets to attenuate inflammation-mediated damage after TBI.
SN - 2041-4889
ER -