Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination DOI Creative Commons
Jinchao Hou, Roberta Magliozzi, Yun Chen

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(13)

Опубликована: Март 25, 2025

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration brain. TREM2 is a receptor that activates microglia, which are crucial for clearing debris and promoting remyelination. Previous studies mouse model demyelination induced by copper-chelating agent Cuprizone (CPZ) have shown stimulation with monoclonal antibody reduces demyelination, while deleting Trem2 gene mice impairs Here, we blocked function acutely an during both remyelination phases CPZ analyzed impact treatment myelination expression single cells. found blocking depleted distinct population microglia high transcription factor MAFB The loss these MAFB-high was linked to impaired generation myelinating oligodendrocytes. Importantly, identified + acute acute-chronic brain lesions from individuals multiple sclerosis (MS), but not inactive lesions. conclude essential maintaining associated repair. This finding has significant implications understanding demyelinating diseases like MS suggests stimulating could be promising therapeutic approach

Язык: Английский

The Alteration of Microglial Calcium Homeostasis in Central Nervous System Disorders: A Comprehensive Review DOI Creative Commons
ATM Hasibul Hasan, Faria Tasnim, Md. Aktaruzzaman

и другие.

Neuroglia, Год журнала: 2024, Номер 5(4), С. 410 - 444

Опубликована: Окт. 21, 2024

Microglia, the unique and motile immune cells of central nervous system (CNS), function as a security guard in maintaining CNS homeostasis, primarily through calcium signaling. The dynamics microglia control important functions such phagocytosis, cytokine release, migration. Calcium dysregulation has been linked to several disorders, like Alzheimer’s disease (AD), Parkinson’s (PD), multiple sclerosis (MS), ischemic stroke (IS). entering channels voltage-gated (VGCCs), store-operated entry (SOCE), transient receptor potential (TRP) is essential for microglial activation pro-inflammatory responses. Under pathological conditions, formation amyloid-β plaques AD, aggregation α-synuclein PD, oxidative stress MS, exacerbates neuroinflammation, mitochondrial dysfunction, neurodegeneration. Therapeutic strategies targeting signaling pathways, using channel blockers antioxidant interventions, show promise alleviating slowing down progression. This review summarizes underlying mechanisms therapeutic benefits restoring balance disorders.

Язык: Английский

Процитировано

10
Gastrodin promotes CNS myelinogenesis and alleviates demyelinating injury by activating the PI3K/AKT/mTOR signaling DOI Creative Commons
Xiaoyu Shi,

Yixi He,

Maofa Ge

и другие.

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

Abstract Demyelination is a common feature of numerous neurological disorders including multiple sclerosis and leukodystrophies. Although myelin can be regenerated spontaneously following injury, this process often inadequate, potentially resulting in neurodegeneration exacerbating dysfunction. Several drugs aimed at promoting the differentiation oligodendrocyte precursor cells (OPCs) have yielded unsatisfactory clinical effects. A recent study has shifted strategy pro-OPC towards enhancing myelinogenesis. In we identified pro-myelinating drug using zebrafish model. Five traditional Chinese medicine monomers gastrodin, paeoniflorin, puerarin, salidroside scutellarin were assessed by bath-application Tg (MBP:eGFP-CAAX) transgenic line 1–5 dpf. Among 5 monomers, only gastrodin exhibited significant pro-myelination activity. We showed that (10 µM) enhanced sheath formation (OL) maturation without affecting number OLs. Gastrodin markedly increased phosphorylation levels PI3K, AKT, mTOR primary cultured OLs via direct interaction with PI3K. Co-treatment PI3K inhibitor LY294002 (5 mitigated gastrodin-induced OL maturation. Furthermore, injection (100 mg·kg −1 ·d , i.p.) effectively facilitated remyelination lysophosphatidylcholine-induced demyelinating mouse model alleviated demyelination experimental autoimmune encephalomyelitis mice. These results identify as promising therapeutic agent for diseases highlight potential screening pro-myelinogenic pharmacotherapy.

Язык: Английский

Процитировано

0
Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination DOI Creative Commons
Jinchao Hou, Roberta Magliozzi, Yun Chen

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(13)

Опубликована: Март 25, 2025

We investigated the role of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in myelin regeneration brain. TREM2 is a receptor that activates microglia, which are crucial for clearing debris and promoting remyelination. Previous studies mouse model demyelination induced by copper-chelating agent Cuprizone (CPZ) have shown stimulation with monoclonal antibody reduces demyelination, while deleting Trem2 gene mice impairs Here, we blocked function acutely an during both remyelination phases CPZ analyzed impact treatment myelination expression single cells. found blocking depleted distinct population microglia high transcription factor MAFB The loss these MAFB-high was linked to impaired generation myelinating oligodendrocytes. Importantly, identified + acute acute-chronic brain lesions from individuals multiple sclerosis (MS), but not inactive lesions. conclude essential maintaining associated repair. This finding has significant implications understanding demyelinating diseases like MS suggests stimulating could be promising therapeutic approach

Язык: Английский

Процитировано

0