Antagonism of ß-arrestins in IL-4-driven microglia reactivity via the Samd4/mTOR/OXPHOS axis in Parkinson's disease.
Sci Adv
; 10(34): eadn4845, 2024 Aug 23.
Article
em En
| MEDLINE
| ID: mdl-39167645
ABSTRACT
Interleukin-4 (IL-4)-exposed microglia acquire neuroprotective properties, but their functions and regulation in Parkinson's disease (PD) are poorly understood. In this study, we demonstrate that IL-4 enhances anti-inflammatory microglia reactivity, ameliorates the pathological features of PD, and reciprocally affects expression of ß-arrestin 1 and ß-arrestin 2 in microglia in PD mouse models. We also show that manipulation of two ß-arrestins produces contrary effects on the anti-inflammatory states and neuroprotective action of microglia induced by IL-4 in vivo and in vitro. We further find that the functional antagonism of two ß-arrestins is mediated through sequential activation of sterile alpha motif domain containing 4 (Samd4), mammalian target of rapamycin (mTOR), and mitochondrial oxidative phosphorylation (OXPHOS). Collectively, these data reveal opposing functions of two closely related ß-arrestins in regulating the IL-4-induced microglia reactivity via the Samd4/mTOR/OXPHOS axis in PD mouse models and provide important insights into the pathogenesis and therapeutics of PD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Transdução de Sinais
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Interleucina-4
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Microglia
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Modelos Animais de Doenças
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Serina-Treonina Quinases TOR
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article