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Cyclophilin inhibitor NIM811 ameliorates experimental allergic encephalomyelitis.

Abstract：

:Cyclophilins have diverse functions that may affect the course of central nervous system (CNS) inflammatory disorders. Anti-inflammatory and neuroprotective mechanisms may be targeted by inhibition of cyclophilin A-dependent and cyclophilin D-dependent functions, respectively. We tested the effect of cyclophilin inhibition on CNS inflammation by administering N-methyl-4-isoleucine-cyclosporin (NIM811) to mice undergoing experimental allergic encephalomyelitis (EAE). Treatment with NIM811 resulted in significant reduction of EAE clinical severity. Analysis of mitochondrial calcium retention capacity and the course of EAE in cyclophilin D knockout mice indicated that the effect of NIM811 on EAE was not entirely cyclophilin D-dependent. NIM811-treated EAE animals showed reduction in interleukin-2 expression and reduction in CNS inflammatory infiltrates. These results indicate that anti-inflammatory rather than neuroprotective mechanisms associated with cyclophilins are likely involved in the mechanism of NIM811 in EAE.

journal_name

J Neuroimmunol

journal_title

Journal of neuroimmunology

authors

Huang ZL,Pandya D,Banta DK,Ansari MS,Oh U

doi

10.1016/j.jneuroim.2017.07.016

subject

Has Abstract

pub_date

2017-10-15 00:00:00

pages

40-48

eissn

0165-5728

issn

1872-8421

pii

S0165-5728(16)30212-0

journal_volume

311

pub_type

杂志文章

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