Anti-CAMK2G polyclonal antibody

Epilepsy is a complex neurological disorder and a significant health problem. The pathogenesis of epilepsy remains obscure in a significant number of patients and the current treatment options are not adequate in about a third of individuals which were known as refractory epilepsies (RE). Network medicine provides an effective approach for studying the molecular mechanisms underlying complex diseases. Here we integrated 1876 disease-gene associations of RE and located those genes to human protein-protein interaction (PPI) network to obtain 42 significant RE-associated disease modules. The functional analysis of these disease modules showed novel molecular pathological mechanisms of RE, such as the novel enriched pathways (e.g., "presynaptic nicotinic acetylcholine receptors", "signaling by insulin receptor"). Further analysis on the relationships between current drug targets and the RE-related disease genes showed the rational mechanisms of most antiepileptic drugs. In addition, we detected ten potential novel drug targets (e.g., KCNA1, KCNA4-6, KCNC3, KCND2, KCNMA1, CAMK2G, CACNB4 and GRM1) located in three RE related disease modules, which might provide novel insights into the new drug discovery for RE therapy.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) has long been implicated in neuronal injury caused by acute ischemia/reperfusion (I/R). However, its precise role and regulatory mechanisms remain obscure. Here, we investigated the role of the CaMKII family in neuronal survival during I/R. Our data indicated that CAMK2D/CaMKII and CAMK2G/CaMKII were selectively upregulated in a time-dependent manner at both transcriptional and protein levels after acute ischemia. Overexpression of CaMKII promoted neuronal survival, while their depletion exacerbated ischemic neuronal death. Similar to CaMKII, knockdown of CAMKII resulted in significant neuronal death after I/R. We further identified CaMKII2 as the subtype that is selectively induced by I/R in primary neurons. The induction of CaMKII was controlled in part by a pair of long non-coding RNAs (lncRNAs), C2dat1 and C2dat2. C2dat2, similar to C2dat1, was upregulated by I/R and cooperated with C2dat1 to modulate CaMKII expression. Knockdown of C2dat1/2 blocked OGD/R-induced CaMKII expression and decreased neuronal survival but did not affect the levels of CaMKII, indicating specific targeting of CAMK2D by C2dat1/2. Mechanistically, I/R-induced CaMKII and CaMKII caused the upregulation of IKK/ and further activation of the NF-B signaling pathway to protect neurons from ischemic damage. Genetically, downregulating p65 subunit of NF-B in mice increased I/R-induced neuronal death by blocking the activity of CaMKII/IKK/IB/NF-B signaling axis. In summary, CaMKII and CaMKII are novel I/R-induced genes that promote neuronal survival during ischemic injury. The upregulation of these CaMKII kinases led to activation of the NF-B signaling pathway, which protects neurons from ischemic damage.