Like smoke rising from the head, the cause of ‘Moyamoya disease’ worsening, which causes cerebrovascular abnormalities, has been discovered.

Research results have shown that the cause of Moyamoya disease, in which cerebral blood vessels gradually narrow and become blocked, worsens because the function of blood vessel cells declines due to mutations in certain genes.

Professor Hong Ji-man’s team (researcher Shin Hee-seon) of the Department of Neurology at Ajou University Hospital has identified that in the background of the serious progression of moyamoya disease, the ‘RNF213 mutant gene’ operates as a mechanism that reduces cell function and causes abnormal proteins to accumulate in the brain blood vessels. It was announced on the 24th. It was found that the vascular endothelial cells of patients with this mutant gene became more seriously ill as they were exposed to stressful environments, such as lack of oxygen and glucose.

Moyamoya disease is a rare and incurable disease in which the arteries that supply blood to the brain gradually narrow and eventually become blocked. When blood supply is insufficient, abnormal microscopic blood vessels grow to make up for it. Because these blood vessels resemble smoke, it is called ‘moyamoya’ disease, which means ‘sharp’ in Japanese. This disease has a particularly high prevalence and family history in Asia, including Korea, China, and Japan. The proportion of patients with the RNF213 mutant gene observed in this study amounts to approximately 80% in Korea and Japan.

Among moyamoya disease patients, the researchers compared the group with normal RNF213 gene (15 patients), the group with mutated RNF213 gene (15 patients), and the general population without the disease (15 patients). In each patient group, we analyzed whether peripheral blood mononuclear cells properly utilized their autophagy ability, which plays a role in removing unnecessary abnormal proteins. As a result of the analysis, it was found that the cells of patients with genetic mutations had reduced function and their autophagy ability was suppressed.

We also confirmed what changes occur when cells are exposed to hypoxia and glucose deficiency, such as in the brain environment of patients with moyamoya disease. As a result of comparing when the RNF213 gene was normal and when it was mutated, more ‘autophagy cysts’, which are observed when abnormal proteins are removed from mutated cells, were observed. Autophagy is a function that plays an important role in removing unnecessary or abnormal proteins from the human body, allowing cells to maintain their original state.

The researchers who analyzed the results explained that when autophagy is suppressed and the function of vascular endothelial cells decreases, abnormal proteins accumulate in the cerebral blood vessels, which reduces cerebral blood flow, making moyamoya disease worse. Professor Hong Ji-man said, “This study is significant in that it is the first to confirm that environmental stress, such as hypoxia, seriously progresses the disease in Moyamoya disease, which has a mutation in the RNF213 gene.” Researcher Shin Hee-seon said, “By identifying the relationship between autophagy and vascular cell function in the peripheral blood cells of actual moyamoya patients, we look forward to the development and clinical application of new drugs in the future.”