Broken Signals Can Trigger Neurodegeneration
Researchers have discovered that a cell receptor widely involved in intracellular calcium signaling can be locked into a closed state by enzyme action, which could lead to reduction of neuron signaling seen in neurodegenerative diseases such as Huntington's and Alzheimer's disease.
According to researchers, transglutaminase type 2-a protein cross-linking enzyme elevated in the cells of patients with neurodegenerative diseases-interacts with the IP3R receptor to lock it in a closed non-functional conformation preventing it from fulfilling its essential calcium-releasing role. They identified a specific amino acid site on the receptor, Gln2746, where the modification takes place.
Findings of the study might open new doors to studies on other functional proteins that are also regulated by conformational charges.
"We think that the mechanism we identified in this study could provide us with a more general model of other diseases both of the brain and other parts of the body, where transglutaminase type 2 is upregulated. We hope that this insight could eventually lead to the development of new drug therapies for a number of neurodegenerative diseases that place a high burden on patients and society," said lead author Katsuhiko Mikoshiba.
The study was published in the Proceedings of the National Academy of Sciences.