Neuroinflammation-Modulating Agent SB1617 Enhances LC3-Associated Phagocytosis to Mitigate Tau Pathology.
ACS Chem Neurosci
; 14(23): 4139-4152, 2023 12 06.
Article
in En
| MEDLINE
| ID: mdl-38014902
ABSTRACT
Tau protein aggregation and propagation in neurons and surrounding microglia are well-known risk factors for neurodegenerative diseases. Therefore, emerging therapeutic strategies that target neuroinflammatory activity in microglia have the potential to prevent tauopathy. Here, we explored the microglia-mediated neuroprotective function of SB1617 against tau aggregation. Our study revealed that SB1617-inactivated pathogenic M1-like microglia, reduced the secretion of pro-inflammatory cytokines via translational regulation, and induced microglial polarization toward the M2 phenotype and phagocytic function. Furthermore, we observed that extracellular pathogenic tau aggregates were eliminated via LC3-associated phagocytosis. The in vivo efficacy of SB1617 was confirmed in mice with traumatic brain injury in which SB1617 exerted neuroprotective effects by reducing pathogenic tau levels through microglia-mediated anti-inflammatory activity. Our results indicated that SB1617-mediated microglial surveillance with LC3-associated phagocytosis is a critical molecular mechanism in the regulation of tau proteostasis. This study provides new insights into tauopathies and directions for developing novel therapies for neurodegenerative diseases.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tauopathies
/
Neuroinflammatory Diseases
Limits:
Animals
Language:
En
Journal:
ACS Chem Neurosci
Year:
2023
Document type:
Article