Findings May Lead to Drugs for Treatment of Neurodegenerative Disease, Alzheimer's Disease
NEW YORK (Sept. 9, 2010) — Neurons are cells in the brain and body that communicate with one another by electrical and chemical signals — like messages traveling along phone lines — but scientists have observed that these cells purposefully hold back their full potential. Now, for the first time, scientists from Weill Cornell Medical College may be able to explain this behavior, but more importantly, how to boost a neuron's signaling.
The promising results published today in the journal Neuron may explain how to unlock a neuron's communication system, which could lead to new drugs for the treatment of neurodegenerative diseases, such as Alzheimer's disease.
"Scientists have observed that the neuron uses only about half of its signaling ability, but, until now, no one understood exactly why this happens or how to augment it," says Dr. Timothy Ryan, senior author of the study and professor of biochemistry at Weill Cornell Medical College in New York City.
Dr. Ryan explains that there is a "resting pool" of cell organelles called vesicles — bubble-like structures located at the ends of the neuron that carry neurotransmitter chemicals. These chemicals move from one neuron to another at a junction between neurons called the synapse. When an electrical signal arrives at the synapse it causes the vesicles to release their chemical, relaying a chemical message to the partnering cell. About 15 years ago scientists discovered that about half of the vesicles were in a "resting state" and never participated in this signaling relay.
"It's as if the vesicles were being held in neutral, immobilized and unable to engage the clutch that would allow them to move forward to deliver their payload," says Dr. Ryan.
The researchers found that they could release the immobile vesicles by blocking a protein called cyclin-dependent kinase 5 (CDK5), which is already known to be involved in brain development. They found that after CDK5 was blocked in rat neurons, almost all of the vesicles could be tapped to take part in the job of relaying the signal.
"But we still didn't understand why this system was in place — why does the brain hold back half the signal?" says Dr. Ryan.
In addition to discovering that blocking CDK5 would unlock the resting vesicles, Dr. Ryan was able to "trick" the pre-synaptic neuron into releasing the rest of the vesicles by simply keeping the neuron quiet for several days using a toxin that blocked the electrical signaling system.
"We believe that the neurons somehow were able to recognize that the signal is not getting through, so it decides to boost the signal by sending in reserve troops," explains Dr. Ryan. "It's as if the neuron has a failsafe system. If the message doesn't get through, there are backups ready to accomplish the mission."
Dr. Ryan hopes that a better understanding of how the neuronal vesicles behave and how to artificially boost neuronal signaling will eventually lead to drugs that may help treat neurodegenerative diseases.
Dr. Sung Hyun Kim from Weill Cornell Medical College is the co-author of this study, supported in part by grants from the National Institutes of Health and a sponsored research agreement with Galenea Corp. Dr. Ryan is a paid consultant and holds equity in Galenea Corp.
Weill Cornell Medical College
Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, Cornell University is the first in the U.S. to offer a M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit www.med.cornell.edu.
Andrew Klein
ank2017@med.cornell.edu