Oct 17, 2002
Why do some nerve cells survive and regrow after injury while others shrink away and die? A new discovery by researchers at Massachusetts General Hospital (MGH) shows that the expression of a particular gene may be responsible for protecting neurons from death. The results, published in the journal Neuron, could lead the way for new treatment strategies for a variety of neurological diseases.
"Turning on the gene named Hsp27 could potentially rescue nerve cells in patients with neurodegenerative conditions such as Lou Gehrig's disease," said principal investigator Clifford Woolf, MD, PhD, of the Neural Plasticity Research Group in the department of anesthesia and critical care at MGH.
Woolf and his colleagues found that young sensory and motor nerve cells die after injury because the heat shock protein 27 gene (Hsp27) is not turned on in these cells. In adult cells however, the gene is expressed. The resulting protein that is produced protects these mature nerve cells from death following an injury.
"As part of normal development, many more neurons are made than are needed," said Woolf, who also is Richard J. Kitz Professor of Anesthesia Research at Harvard Medical School. "So some must be pruned away by essentially committing cell suicide, a phenomenon known as programmed cell death. It seems that Hsp27 is turned off to allow for this normal developmental process."
Woolf explained that once an individual reaches adulthood, nerve cells in the body are permanent and irreplaceable. "That's why it's important to have a repair mechanism for older neurons," he said. The protein made by the Hsp27 gene blocks cell suicide from taking place following injury, rescuing injured cells. For example, cells expressing the Hsp27 protein acquire resistance to excessive heat, chemical stress, and toxins. Hsp27 directly inhibits the cellular proteins that trigger programmed cell death.
In laboratory dishes and in rat models, Woolf and his team showed that,
if the Hsp27 gene is delivered to young nerve cells using gene therapy
with viral vectors, the cells are able to survive injury just as well as
older nerve cells. Equally, if the gene is switched off in adults, those
cells will die. "Hopefully, therapy that prevents cell death by delivering
genes like Hsp27 will someday find its way into the clinic," said Woolf.
"Patients with Lou Gehrig's disease, for example, suffer a progressive
death of their motor neurons leading to paralysis. If Hsp27 were able to
prevent the death of the neurons in these patients, it would offer the
possibility of new therapy, something we plan to test." This article was
prepared by Genomics and Genetics Weekly editors from staff and other reports.
© Copyright 2002, Genomics and Genetics Weekly