Neuronal necrosis induced by calcium overload causes devastating brain dysfunction in diseases such as stroke and brain trauma. It has been considered a stochastic event lacking genetic regulation, and pharmacological means to suppress neuronal necrosis are lacking. Using a Drosophila model of calcium overloading, we found JIL-1/mitogen- and stress-activated protein kinase 1/2 is a regulator of neuronal necrosis through phosphorylation of histone H3 serine 28 (H3S28ph). Further, we identified its downstream events including displacement of polycomb repressive complex 1 (PRC1) and activation of Trithorax (Trx). To test the role of JIL-1/PRC1/Trx cascade in mammals, we studied the necrosis induced by glutamate in rat cortical neuron cultures and rodent models of brain ischemia and found the cascade is activated in these conditions and inhibition of the cascade suppresses necrosis in vitro and in vivo. Together, our research demonstrates that neuronal necrosis is regulated by a chromatin-modifying cascade, and this discovery may provide potential therapeutic targets and biomarkers for neuronal necrosis.
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 October 2014.
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#4,381,647
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Outputs from Proceedings of the National Academy of Sciences of the United States of America
#44,290
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Outputs of similar age
#37,639
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Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#491
of 911 outputs
Altmetric has tracked 34,364,397 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 118,931 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 40.1. This one has gotten more attention than average, scoring higher than 62% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 281,813 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 911 others from the same source and published within six weeks on either side of this one. This one is in the 45th percentile – i.e., 45% of its contemporaries scored the same or lower than it.
