Moyamoya disease is an intractable cerebrovascular disease of unknown cause that is common in East Asia (Japan, China, and Korea).The internal carotid artery, which is the main blood supply channel to the brain, is narrowed and occluded, and ischemia develops hazy, smoke-like capillaries in the skull.It may cause ischemic attack / cerebral infarction and is regarded as one of the serious designated intractable diseases.
So far, mutations in the mysterin gene have been found as risk factors for moyamoya disease, but it was unclear how they work and what kind of dysfunction is caused by mutations in moyamoya disease.
This time, a joint research by Kyoto Sangyo University, Aoyama Gakuin University, and Hokkaido University revealed that mysterin is a regulator of fat metabolism.Mysterin is localized in the intracellular fat storage site, "lipid droplets," and has the function of protecting lipid droplets from lipolytic enzymes and promoting fat accumulation.
Until now, no attention has been paid to the relationship between moyamoya disease and fat metabolism, but this discovery suggests that moyamoya disease may be caused by an imbalance in metabolism.
Furthermore, when we investigated the dysfunction of mysterin due to the mutation in moyamoya disease, we found that the ubiquitin ligase mutation in white moyamoya disease patients caused the mysterin to drop out of the lipid droplets and form abnormal aggregates. Both have been shown to be the cause of moyamoya disease.On the other hand, the R4810K mutation in East Asian moyamoya disease patients did not show any dysfunction, but the mutation carrier is 100 times more likely to be morbid, so it is a mistake that the mutation is an important risk factor. No.That is, it can cause anomalies similar to Caucasian mutations if there are any additional factors.
Further elucidation is awaited in the future as to how the two abnormalities (droplet of mysterin from lipid droplets and agglutination) are involved in the process of developing moyamoya disease.
Paper information:[The Journal of Cell Biology] The AAA + ATPase / ubiquitin ligase mysterin stabilizes cytoplasmic lipid droplets
