Researchers have identified a molecular pathway that can be a potential therapeutic target for Down's syndrome, the most frequent cause of mental retardation.
The research in Salk Institute for Biological Studies, showed that synaptojanin-1, a central component of the pathway, is essential to production of glia, brain cells that act as neurons' personal assistants.
AdvertisementDown's syndrome, spinal cord injury, Alzheimer's disease, and stroke all are linked by an overproduction of glia.
"The discovery of this molecular signaling pathway promises to completely change the way we think about central nervous system maladies, allowing the development of drugs that inhibit glial proliferation and improve the prognosis of patients with a host of devastating conditions," said Salk professor David Schubert, who heads the Cellular Neurobiology Laboratory.
With the help of new mass spectrometry technique and stem cells that can be made to produce either neurons or glia, the researchers led by Federico Herrera, Ph.D., a senior scientist in the Cellular Neurobiology Laboratory, identified a molecular signaling pathway that is required for the production of glial cells.
They later studied the pathway in Down's syndrome patients and a mouse model of the condition.
The findings revealed that the level of a protein called synaptojanin-1, which is encoded in chromosome 21, is much higher in both and is strongly correlated with a greater number of glial cells.
"Given the required balance between the numbers of neurons and glia in a normal brain, an excess of glia may contribute to the cognitive deficits that characterize Down's syndrome," said Herrera.
Moreover, a particular part of the Synaptojanin-1 molecule was responsible for generating glia.
"This is a critical first step to identifying drugs that specifically block the excess proliferation of glial cells associated with Down's syndrome and perhaps promote the production of more neurons," Herrera added.
The newly identified molecular pathway may also have implications for the onset of glioblastoma, the most common and malignant type of brain tumor.
The findings are published Cell Death and Differentiation.
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