Inhibition of T cell infiltration and soluble TNF signaling is neuroprotective in the alpha-synuclein overexpressing mouse model of Parkinson’s disease DOI

Adriana Tavira,

Leyre Basurco, Miguel Angel Abellanas

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract Modulation of the neuroinflammatory response is emerging as an interesting approach for treatment Parkinson´s disease (PD). In this study we have used adeno-associated virus (AAV9) to overexpress alpha-synuclein (αSyn) in substantia nigra pars compacta mice induce a dose-dependent neuronal loss. Our results show that αSyn overexpression induces CD4+ T cell infiltration with Th1 (IFNγ+TNFα+) phenotype ventral midbrain. Inhibiting fingolimod (FTY720) or blocking soluble TNF signaling XPro1595 improved motor function and preserved dopaminergic neurons. These treatments showed therapeutic efficacy chronic mouse model generated lower AAV9 titers, highlighting potential targeting neuroinflammation PD. findings suggest cells contribute αSyn-induced neurodegeneration immune modulation may be viable strategy support further exploration neuroinflammation-targeting therapies

Language: Английский

Identification and validation of Atp5f1c in CD4+ T cell as a hub protein in Parkinson's disease DOI
Guoqing Wang, Yuanyuan Wang,

Xiao-lan Tang

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 297, P. 139858 - 139858

Published: Jan. 14, 2025

Language: Английский

Citations

0
The cGAS-STING pathway drives neuroinflammation and neurodegeneration via cellular and molecular mechanisms in neurodegenerative diseases DOI Creative Commons
Yuxin Zhang, Meijuan Zou, Hao Wu

et al.

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

Citations

3
Inhibition of T cell infiltration and soluble TNF signaling is neuroprotective in the alpha-synuclein overexpressing mouse model of Parkinson’s disease DOI

Adriana Tavira,

Leyre Basurco, Miguel Angel Abellanas

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract Modulation of the neuroinflammatory response is emerging as an interesting approach for treatment Parkinson´s disease (PD). In this study we have used adeno-associated virus (AAV9) to overexpress alpha-synuclein (αSyn) in substantia nigra pars compacta mice induce a dose-dependent neuronal loss. Our results show that αSyn overexpression induces CD4+ T cell infiltration with Th1 (IFNγ+TNFα+) phenotype ventral midbrain. Inhibiting fingolimod (FTY720) or blocking soluble TNF signaling XPro1595 improved motor function and preserved dopaminergic neurons. These treatments showed therapeutic efficacy chronic mouse model generated lower AAV9 titers, highlighting potential targeting neuroinflammation PD. findings suggest cells contribute αSyn-induced neurodegeneration immune modulation may be viable strategy support further exploration neuroinflammation-targeting therapies

Language: Английский

Citations

0