Neuregulin 1 (NRG1) and ErbB4, critical neurodevelopmental genes, are implicated in schizophrenia, but the mediating mechanisms are unknown. Here we identify a genetically regulated, pharmacologically targetable, risk pathway associated with schizophrenia and with ErbB4 genetic variation involving increased expression of a PI3K-linked ErbB4 receptor (CYT-1) and the phosphoinositide 3-kinase subunit, p110δ (PIK3CD). In human lymphoblasts, NRG1-mediated phosphatidyl-inositol,3,4,5 triphosphate [PI(3,4,5)P3] signaling is predicted by schizophrenia-associated ErbB4 genotype and PIK3CD levels and is impaired in patients with schizophrenia. In human brain, the same ErbB4 genotype again predicts increased PIK3CD expression. Pharmacological inhibition of p110δ using the small molecule inhibitor, IC87114, blocks the effects of amphetamine in a mouse pharmacological model of psychosis and reverses schizophrenia-related phenotypes in a rat neonatal ventral hippocampal lesion model. Consistent with these antipsychotic-like properties, IC87114 increases AKT phosphorylation in brains of treated mice, implicating a mechanism of action. Finally, in two family-based genetic studies, PIK3CD shows evidence of association with schizophrenia. Our data provide insight into a mechanism of ErbB4 association with schizophrenia; reveal a previously unidentified biological and disease link between NRG1-ErbB4, p110δ, and AKT; and suggest that p110δ is a previously undescribed therapeutic target for the treatment of psychiatric disorders.
It’s really hard to decipher these med reports, isn’t it?
you got that right
Anything but atypical antipsychotics please!
Inhibition of p110δ is possibly a new target to treat schizophrenia. The drug might reverse schizophrenia symptoms, which might be the treatment for the disease.
what are the side effects? it sounds like pretty serious stuff
It was demonstrated in mice model
so its like 15 years away basically if ever
It’s worth waiting for
If the treatment will be able to at least partially improve cognitive function it will be awesome.
Isn’t this from summer 2012? When I was in high school? Kind of dated, don’t you think? Maybe doesn’t belong in the news section.
It is really big news but nobody discussed it
There’s newer articles but they are to complicated so I thought I would present proper articles
are there any articles from 2016 and 2017?
On ncbi discussing p110δ as possible target for a drug