Jan. 19, 2004 NEW BRUNSWICK/PISCATAWAY, N.J. – Rutgers researchers have discovered what could be the newest target for drugs in the treatment of memory and learning disabilities as well as diseases such as Alzheimer's and fetal alcohol syndrome: a protein known as cypin.
Cypin is found throughout the body, but in the brain it regulates nerve cell or neuron branching. Branching or dendrite growth is an important process in normal brain function and is thought to increase when a person learns. A reduction in branching is associated with certain neurological diseases.
"The identification of cypin and understanding how it works in the brain is particularly exciting since it opens up new avenues for the treatment of serious neurological disorders," said principal investigator Bonnie Firestein, assistant professor of cell biology and neuroscience at Rutgers, The State University of New Jersey. "This paves the way to designing new drugs that could target this protein molecule."
Proteins or the genes that code for them have become the targets of choice for developing precisely focused, effective new drug therapies – one of the outcomes of the many revelations provided by the Human Genome Project.
Firestein first identified and isolated cypin in 1999 during her postdoctoral research. She is currently focusing on how it works in the hippocampus, a structure in the brain associated with the regulation of emotions and memory.
"We knew that cypin existed elsewhere in the body where it performs other functions, but no one knew why it was present in the brain," Firestein. Her new research determined that cypin in the brain works as an enzyme involved in shaping neurons.
"One end of a neuron looks like a tree and, in the hippocampus, cypin controls the growth of its branches," she explained. "An increase in the number of branches provides additional sites where a neuron can receive information that it can pass along, enhancing communication."
Maxine Chen, a graduate student in Firestein's laboratory, helped substantiate the connection between cypin and dendrite growth. When she looked closely at neurons in the lab, she found cypin only in certain neurons – "neurons that tended to be more fuzzy," as she described those with increased dendrites. Stimulating neurons in a dish also produced an increase in the protein overall. This has been shown to increase dendrite growth.
Fellow graduate student Barbara Akum further verified the connection between the protein and branching. She used a new molecular technique developed by Samuel Gunderson, a Rutgers assistant professor of molecular biology and biochemistry. With this new tool, Akum reduced the expression of cypin and observed a consequent decrease in branching.
"We also found something else that is really exciting," said Firestein, referring to the molecular mechanics by which cypin affects dendrite growth. Cypin appears to act as a glue that cements other molecules together into long chain structures that extend through the branches of a dendrite as a skeleton.
"Cypin works on tubulin, a protein that is a structural building block of the dendrite skeleton," explained Firestein. "If you just take our purified protein and mix it with tubulin in a test tube, the cypin on its own will actually cause these skeletal structures to grow."
A paper presenting this research will appear in Nature Neuroscience online beginning (Sunday) Jan. 19.
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