التفاصيل البيبلوغرافية
| العنوان: |
HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage |
| المؤلفون: |
Loppi, S., Kolosowska, N., Kärkkäinen, O., Korhonen, P., Huuskonen, M., Grubman, A., Dhungana, H., Wojciechowski, S., Pomeshchik, Y., Giordano, M., Kagechika, H., White, A., Auriola, S., Koistinaho, J., Landreth, G., Hanhineva, K., Kanninen, K., Malm, T. |
| المساهمون: |
Neuroscience Center, University of Helsinki |
| بيانات النشر: |
ACADEMIC PRESS INC ELSEVIER SCIENCE |
| سنة النشر: |
2020 |
| المجموعة: |
Helsingfors Universitet: HELDA – Helsingin yliopiston digitaalinen arkisto |
| مصطلحات موضوعية: |
Stroke, Neuroinflammation, Microglia, Nuclear receptors, Metabolic profiling, MIDDLE CEREBRAL-ARTERY, FACTOR-KAPPA-B, ORPHAN NUCLEAR RECEPTORS, NITRIC-OXIDE SYNTHASE, IMMEDIATE-EARLY GENES, MOUSE STROKE MODEL, RESONANCE-SPECTROSCOPY, MOLECULAR-MECHANISMS, PHOSPHOLIPASE A(2), OXIDATIVE STRESS, 3112 Neurosciences |
| الوصف: |
Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component. ; Peer reviewed |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
We thank Ms. Mirka Tikkanen for excellent technical assistance. This study was supported by the Academy of Finland.; Loppi , S , Kolosowska , N , Kärkkäinen , O , Korhonen , P , Huuskonen , M , Grubman , A , Dhungana , H , Wojciechowski , S , Pomeshchik , Y , Giordano , M , Kagechika , H , White , A , Auriola , S , Koistinaho , J , Landreth , G , Hanhineva , K , Kanninen , K & Malm , T 2018 , ' HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage ' , Brain, Behavior, and Immunity , vol. 73 , pp. 670-681 . https://doi.org/10.1016/j.bbi.2018.07.021Test; ORCID: /0000-0001-6559-1153/work/53186001; 85050850373; c8eb4722-9f02-417e-807b-7716c5df1bb0; http://hdl.handle.net/10138/308993Test; 000445440900064 |
| الإتاحة: |
http://hdl.handle.net/10138/308993Test |
| حقوق: |
openAccess ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: |
edsbas.6ED22690 |
| قاعدة البيانات: |
BASE |
