Abstract：
:Previous studies in our lab revealed that chemical zinc chelation or zinc transporter 3 (ZnT3) gene deletion suppresses the clinical features and neuropathological changes associated with experimental autoimmune encephalomyelitis (EAE). In addition, although protective functions are well documented for AMP-activated protein kinase (AMPK), paradoxically, disease-promoting effects have also been demonstrated for this enzyme. Recent studies have demonstrated that AMPK contributes to zinc-induced neurotoxicity and that 1H10, an inhibitor of AMPK, reduces zinc-induced neuronal death and protects against oxidative stress, excitotoxicity, and apoptosis. Here, we sought to evaluate the therapeutic efficacy of 1H10 against myelin oligodendrocyte glycoprotein 35-55-induced EAE. 1H10 (5 μg/kg) was intraperitoneally injected once per day for the entire experimental course. Histological evaluation was performed three weeks after the initial immunization. We found that 1H10 profoundly reduced the severity of the induced EAE and that there was a remarkable suppression of demyelination, microglial activation, and immune cell infiltration. 1H10 also remarkably inhibited EAE-associated blood-brain barrier (BBB) disruption, MMP-9 activation, and aberrant synaptic zinc patch formation. Furthermore, the present study showed that long-term treatment with 1H10 also reduced the clinical course of EAE. Therefore, the present study suggests that zinc chelation and AMPK inhibition with 1H10 may have great therapeutic potential for the treatment of multiple sclerosis.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Choi BY,Jeong JH,Eom JW,Koh JY,Kim YH,Suh SWdoi
10.3390/ijms21093375subject
Has Abstractpub_date
2020-05-10 00:00:00issue
9issn
1422-0067pii
ijms21093375journal_volume
21pub_type
杂志文章abstract：:Rates of loco-regional recurrence and distant metastasis remain high among head and neck squamous cell carcinoma (HNSCC) patients, despite advancing cancer treatment modalities and therapeutic agents. One area that has generated considerable interest is the immune landscape of the tumour, heralding a wave of immune ch...
journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2013-07-11 00:00:00
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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journal_title：International journal of molecular sciences
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更新日期：2018-10-01 00:00:00
