Powerful Function of Single Protein

The study shows how brain cells talk to each other through these signals, relaying thoughts, feelings and action, and this powerful molecule plays a crucial role in regulating effective communication.

In the study, the investigators also suggest how the widely used pain drug Lyrica might work. The alpha 2 delta protein is the target of this drug and the new work suggests an approach to how other drugs could be developed that effectively twist particular neurotransmitter spigots on and off to treat neurological disorders.

"We are amazed that any single protein has such power," says the study's lead investigator Doctor Timothy A. Ryan. "It is indeed rare to identify a biological molecule's function that is so potent, that seems to be controlling the effectiveness of neurotransmission."

The researchers found that alpha 2 delta determines how many calcium channels will be present at the synaptic junction between neurons. The transmission of chemical signals is triggered at the synapse by the entry of calcium into these channels, so the volume and speed of neurotransmission depends on the availability of these channels.

Researchers discovered that taking away alpha 2 delta from brain cells prevented calcium channels from getting to the synapse. "But if you add more alpha 2 delta, you can triple the number of channels at synapses," Ryan says. "This change in abundance was tightly linked to how well synapses carry out their function, which is to release neurotransmitters."

Before this study, it was known that Lyrica, which is used for neuropathic pain, seizures and fibromyalgia, binds to alpha 2 delta, but little was understood about how this protein works to control synapses.

"We are looking under the hood of these machines for the first time," he says. "Many neurological diseases are considered to arise from pathologies of synaptic function. The synapse is so complex, at least a few thousand genes control how they work. Repairing them through treatment requires that we understand how they work."

MEDICA.de; Source: Weill Cornell Medical College