The metastasis-promoting S100A4 protein confers neuroprotection in brain injury
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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The metastasis-promoting S100A4 protein confers neuroprotection in brain injury. / Dmytriyeva, Oksana; Pankratova, Stanislava; Owczarek, Sylwia; Sonn, Katrin; Soroka, Vladislav; Ridley, Christina M; Marsolais, Alexander; Lopez-Hoyos, Marcos; Ambartsumian, Noona; Lukanidin, Eugene; Bock, Elisabeth; Berezin, Vladimir; Kiryushko, Dar'Ya.
I: Nature Communications, Bind 3, Nr. 1197, 13.11.2012, s. 1197.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - The metastasis-promoting S100A4 protein confers neuroprotection in brain injury
AU - Dmytriyeva, Oksana
AU - Pankratova, Stanislava
AU - Owczarek, Sylwia
AU - Sonn, Katrin
AU - Soroka, Vladislav
AU - Ridley, Christina M
AU - Marsolais, Alexander
AU - Lopez-Hoyos, Marcos
AU - Ambartsumian, Noona
AU - Lukanidin, Eugene
AU - Bock, Elisabeth
AU - Berezin, Vladimir
AU - Kiryushko, Dar'Ya
PY - 2012/11/13
Y1 - 2012/11/13
N2 - Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain unclear. Here we show that the S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes. Genetic deletion of S100A4 exacerbates neuronal loss after brain trauma or excitotoxicity, increasing oxidative cell damage and downregulating the neuroprotective protein metallothionein I+II. We identify two neurotrophic motifs in S100A4 and show that these motifs are neuroprotective in animal models of brain trauma. Finally, we find that S100A4 rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10 receptor. Our data introduce S100A4 as a therapeutic target in neurodegeneration, and raise the entire S100 family as a potentially important factor in central nervous system injury.
AB - Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain unclear. Here we show that the S100A4 protein, mostly studied in cancer, is overexpressed in the damaged human and rodent brain and released from stressed astrocytes. Genetic deletion of S100A4 exacerbates neuronal loss after brain trauma or excitotoxicity, increasing oxidative cell damage and downregulating the neuroprotective protein metallothionein I+II. We identify two neurotrophic motifs in S100A4 and show that these motifs are neuroprotective in animal models of brain trauma. Finally, we find that S100A4 rescues neurons via the Janus kinase/STAT pathway and, partially, the interleukin-10 receptor. Our data introduce S100A4 as a therapeutic target in neurodegeneration, and raise the entire S100 family as a potentially important factor in central nervous system injury.
KW - Amino Acid Motifs
KW - Animals
KW - Brain Injuries
KW - Cell Death
KW - Cytoprotection
KW - Female
KW - Gene Deletion
KW - HEK293 Cells
KW - Humans
KW - Janus Kinases
KW - Kainic Acid
KW - Mice
KW - Mice, Inbred C57BL
KW - Neoplasm Metastasis
KW - Neurons
KW - Neuroprotective Agents
KW - Neurotoxins
KW - Oxidative Stress
KW - Peptides
KW - Rats
KW - Receptors, Interleukin-10
KW - S100 Proteins
KW - STAT Transcription Factors
KW - Seizures
KW - Up-Regulation
U2 - 10.1038/ncomms2202
DO - 10.1038/ncomms2202
M3 - Journal article
C2 - 23149742
VL - 3
SP - 1197
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1197
ER -
ID: 45118515