Interferon Regulatory Factors as a Potential Therapeutic Target for Neuroinflammation: A Focus on Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2906 - 2906

Published: March 23, 2025

Interferon Regulatory Factors (IRFs) are critical modulators of immune and inflammatory responses, yet their roles in Alzheimer's disease (AD) other neurodegenerative disorders remain incompletely understood. While IRFs recognized for regulatory functions neuroinflammation, microglial activation, neuronal survival, dual as both drivers pathological inflammation mediators neuroprotective pathways underscore a sophisticated paradox disorders. This review aims to synthesize current evidence on IRF-mediated neuroinflammation AD related diseases, focusing the multifaceted key IRF family members, including IRF1, IRF3, IRF7. We critically evaluate divergent roles: IRF1 instance, exacerbate neuroinflammatory cascades amyloid-beta (Aβ) pathology AD, whereas IRF7 may paradoxically suppress under specific conditions. Additionally, we explore dysregulation Parkinson's disease, multiple sclerosis, amyotrophic lateral Huntington's emphasizing shared distinct mechanisms across Restoring balance through genetic manipulation, small-molecule inhibitors, or microbiome-derived could attenuate enhance Aβ clearance, protect integrity. Ultimately, this work provides framework future research harness signaling development precision therapies diseases.

Language: Английский

The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 202, P. 106710 - 106710

Published: Oct. 28, 2024

Neurodegenerative diseases (NDs) are a type of common chronic progressive disorders characterized by damage to specific cell populations in the nervous system, ultimately leading disability or death. Effective treatments for these still lacking, due limited understanding their pathogeneses, which involve multiple cellular and molecular pathways. The triggering an immune response is feature neurodegenerative disorders. A critical challenge intricate interplay between neuroinflammation, neurodegeneration, responses, not yet fully characterized. In recent years, cyclic GMP-AMP synthase (cGAS)-stimulator interferon gene (STING) pathway, crucial intracellular DNA sensing, has gradually gained attention. However, roles this pathway within types such as cells, glial neuronal its contribution ND pathogenesis, remain elucidated. review, we systematically explore how cGAS-STING signaling links various with related effector pathways under context NDs multifaceted therapeutic directions. We emphasize discovery condition-dependent heterogeneity integral diverse responses potential targets. Additionally, review pathogenic role activation Parkinson's disease, ataxia-telangiectasia, amyotrophic lateral sclerosis. focus on complex bidirectional Alzheimer's Huntington's sclerosis, revealing double-edged nature disease progression. objective elucidate pivotal pathogenesis catalyze new insights facilitating development novel strategies.

Language: Английский

CD33 Ameliorates Surgery-Induced Spatial Learning and Memory Impairments Through TREM2

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский