Study of pathogenesis caused by hypouricemia in multiple system atrophy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09805
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Yokohama City University
• Principal Investigator: KOYANO Shigeru 横浜市立大学, 医学研究科, 客員教授 (50315818)
• Co-Investigator(Kenkyū-buntansha): 田中 章景 横浜市立大学, 医学研究科, 教授 (30378012) ; 多田 美紀子 横浜市立大学, 医学部, 助教 (30722467)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 多系統萎縮症 / 尿酸 / 酸化ストレス

Outline of Final Research Achievements

The relationship between neurological diseases and uric acid levels has been reported. Especially for diseases associated with oxidative stress, low levels of uric acid, which has an antioxidant effect, may be associated with the pathogenesis. Multiple system atrophy(MSA) is a disease whose pathological mechanism is associated with oxidative stress. In this study, we analyzed the involvement of uric acid in MSA from a clinical and pathological perspective. Examination of the relationship between serum and cerebrospinal fluid uric acid levels and various clinical data showed that the higher the uric acid level, the slower the progression of the disease. From a neuropathological study, uric acid immunoreactivity was weak in general part in brain of MSA. By contrast, dityrosine immunoreactivity in MSA was prominently observed in neurons, glia are related to the pathological lesions of MSA. These observations suggest the relevance of tyrosine oxidative stress in the pathomechanism of MSA.

Free Research Field

神経内科

Academic Significance and Societal Importance of the Research Achievements

本研究を通じ、活性酸素に関わる神経疾患である多系統萎縮症が低尿酸血症による抗酸化作用の低下によって病態形成に係わることを明らかにすることは極めて重要な意義を持ち、これまで明らかにされなかった多系統萎縮症の病態解明へ一歩になるとともに、他の活性酸素が関連する神経疾患の共通の病態解明への手がかりになることが予想される。さらに、病態に尿酸トランスポーターが関与していることを利用すれば、多系統萎縮症の新規治療法開発への希望につながる可能性がある。