The Role of Astrocyte BMP Signaling in Fragile X Syndrome
Nicola Allen, PhD
Salk Institute for Biological Studies
San Diego, California
2021 Grant Funding: $90,000
University Total Funding: $180,000
Astrocytes are star-shaped cells that make up one fifth of all cells in the human brain. Recently researchers found a specific pathway in astrocytes that is overactive in Fragile X syndrome, and they hope to bring this pathway back to normal with a drug.
With this grant, the team will try to correct the pathway in Fragile X mice. The hope is that they will find a new potential treatment approach for Fragile X syndrome.
By James Deng
Astrocytes are star-shaped cells that constitute around one fifth of all cells in the human brain. Each astrocyte ensheaths thousands of neuron-to-neuron contacts (synapses), and this proximity enables astrocytes to closely tailor the synaptic environment both in health and disease. Emerging work has shown astrocytes not only to promote brain homeostasis, but also to release specific factors at distinct timepoints to guide development, maturation, and breakdown of synapses.
Most research in Fragile X syndrome has focused on changes in neurons, but astrocytes have increasingly been shown to play a role. Growing typically developing neurons with the factors released from Fragile X astrocytes leads the neurons to display alterations similar to findings in Fragile X patients. Recently, we found a pathway— the bone morphogenetic protein (BMP) signaling pathway—that is activated in Fragile X astrocytes and is responsible for many of the changes in astrocyte-released factors specific to Fragile X.
This project aims to target the BMP pathway in astrocytes: We will ask whether deactivating this pathway can improve multiple characteristics of Fragile X mice. Using methods including genetics, viruses, and drugs, we will dissect this pathway and characterize its significance to Fragile X. We will also determine which specific astrocyte released factors are changed in Fragile X, so as to generate leads for potential therapeutic targets.