A Florida State University researcher has received a five-year, $1.8 million grant from the National Institutes of Health to study potential molecular therapies for schizophrenia.
The human brain’s 10 billion nerve cells communicate by transmitting signals through tiny connections known as synapses. Disruptions in those transmissions are an underlying cause of schizophrenia and other neuropsychiatric diseases.
This new grant will allow Yi Zhou, associate professor of biomedical sciences at FSU’s College of Medicine, to study a brain protein that may be critical in maintaining proper synaptic transmission.
Zhou previously found that inhibiting a protein called 14-3-3 also inhibits synaptic function in the brain. Inhibiting 14-3-3 disrupts nerve cell signals and brain circuitry, leading to schizophrenia-associated behaviors such as social withdrawal, hyperactivity and learning and memory deficits in mouse models.
“This 14-3-3 family protein is very abundant in the brain, and nobody really knows what exactly it does,” Zhou said. “We do know it binds to other proteins and modulates the function of those proteins. We are trying to figure out what it regulates that leads to synaptic deficits and behavior deficits.”
Restoring function in this regulatory protein could potentially serve as a therapy for schizophrenia down the line. Schizophrenia patients may suffer from a wide range of symptoms — including disorganized speech and behavior as well as hallucinations and delusions associated with psychosis, a detachment from external reality.
“Right now, the only treatment we have for schizophrenia is for psychosis,” Zhou said. “There’s no cure for other symptoms because we don’t really understand the neurocircuitry or neurobiology behind them. We are trying to figure out what causes the disease. Is there a better molecular target we can find to treat it in the future?”
Because nerve cells don’t work in isolation, scientists strive to understand whole brain circuits and network activity in different regions of the brain. One goal of Zhou’s project is pinpointing where 14-3-3 originates and following its path of protein interactions. That may help identify molecular pathways that can be specifically targeted by drug therapy.
“We are trying to address the fundamental questions to understand the neurobiological, molecular, synaptic and circuit basis. Can we find something wrong that can translate to therapy in the future? This 14-3-3 protein is just one of the keys to open the door.”