Fragile X, Down Syndrome Involve Similar Pathways

Mental disabilities stemming from Fragile X and Down syndrome involve similar molecular pathways, according to a new study published in The EMBO Journal.

Both disorders are characterized by problems with the processes that regulate the way nerve cells develop dendritic spines—the small protrusions on the surface of nerve cells that are vital for communication in the brain.

“We have shown for the first time that some of the proteins altered in Fragile X and Down syndromes are common molecular triggers of intellectual disability in both disorders,” said Kyung-Tai Min, a professor at Indiana University and the Ulsan National Institute of Science and Technology in Korea.

“Specifically, two proteins interact with each other in a way that limits the formation of spines or protrusions on the surface of dendrites.”

“These outgrowths of the cell are essential for the formation of new contacts with other nerve cells and for the successful transmission of nerve signals. When the spines are impaired, information transfer is impeded and mental retardation takes hold,” he said.

Two of the most common genetic causes of intellectual disability are Fragile X and Down syndromes.

Fragile X syndrome is triggered by a single gene mutation that prevents the production of a protein needed for proper neural development (Fragile X mental retardation protein). For Down syndrome to occur, all or a part of a third copy of chromosome 21 must be present.

Although each syndrome is due to a separate genetic difference, the researchers identified a shared molecular pathway in mice that triggers intellectual disability in both disorders.

Down syndrome mice models have difficulties with memory and brain function, and the development of the heart is often compromised, symptoms that are also observed in humans with Down syndrome.

“We believe these experiments provide an important step forward in understanding the multiple roles of DSCR1 in neurons and in identifying a molecular interaction that is closely linked to intellectual disability for both syndromes,” said Min.

Source:  The EMBO Journal