Research targets snapin as drug target
dendrite, patterning, have expressed delight to the protein's
possibilities as a viable drug target in therapies aimed at
learning and memory disorders.
The protein represents the creation of an important point of entry for early intervention with therapeutic drugs. In determining how different branching patterns correlate with specific disorders as well as how these dissimilar patterns occur, the possibility of a targeted treatment becomes a distinct reality.
Researchers from The State University of New Jersey examined the role of the protein snapin. When snapin binds to cypin, another protein that regulates dendrite numbers, they found that cypin works on tubulin, a protein that is a structural building block of the dendrite skeleton. Tubulin is crowded out, resulting in fewer dendrites assembling and more branching occurring.
Dendrites are the input centres of neurons -- where nerve cells receive information that they pass on to another nerve cell or to the brain. When there is an abnormal decrease in dendrite branches, there are fewer sites to receive information and communication may be impeded.
Individuals with disorders such as autism and Rett syndrome display not only fewer branches, but also show two quite different dendrite patterns. The researchers next step was to overexpress snapin in hippocampal neurons in the lab.
They found that the number of primary dendrites growing out of the cell body decreased, but many more secondary dendrites branched off them.
"It's not just how many branches there are, but where they are and the pattern they form," said Bonnie Firestein, an assistant professor in Rutgers' department of cell biology and neuroscience.
"The patterning actually affects the way a cell signals and understanding the patterning could be just as important as understanding how many branches are there. Ultimately, this could lead to new drugs designed to modulate the patterning activity," she added.
While these proteins have other functions in the nerve cell environment and elsewhere in the body, the significance is not just in identifying snapin as a protein that shapes the dendrites, but also in pinpointing a drug target where one can regulate the interaction of snapin with cypin.
"We need to change cypin's function for branching but not its other functions," said Firestein.
"Rather than a drug that blocks cypin, we need a drug that affects the binding between the cypin and snapin. This is easier to design and cypin can still function with the other proteins it binds to."
Firestein commented that the next step was to build "a core pathway of dendric branching," - a sequence of steps, each affecting the next, with cypin at the centre.
"Our pathway says cypin does this; now what regulates cypin? Here snapin has a role. And what does snapin regulate?" said Firestein. "Our hope is in ten years, we will have a whole pathway mapped out so that we can target different points in the pathway with new drugs."
