Pathological and cytological sesearch of neurodegenerative diseases and earch for therapeutic drug candidates based on OPTN dysfunction

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18383
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kyoto University
• Principal Investigator: ayaki takashi 京都大学, 医学研究科, 特定病院助教 (60749555)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: optineurin / NF-кB / multiple proteinopathy / 神経細胞死 / NLRP3インフラマソーム / ミクログリア / 顆粒空砲変性 / 直鎖型ユビキチン

Outline of Final Research Achievements

Through the elucidation of OPTN-mediated autophagy and neuroinflammation signals, we examined the pathogenesis of ALS, Alzheimer's disease and multiple system atrophy. The role of autophagy in ALS has been reported by the presence of multiple protein aggregates in ALS. As for neuroinflammatory signals, we confirmed and reported that phosphorylated p65 (an active form of the NF kappa B signal molecule), is aggregated in the hippocampus of Alzheimer's disease and ALS-OPTN. In addition, we examined NLRP3 inflammasome-related proteins in multiple system atrophy microglia in autopsied brains and reported the relationship between α-synuclein and NLRP3 inflammasome-related protein-positive microglia.

Free Research Field

神経病理学

Academic Significance and Societal Importance of the Research Achievements

OPTNに関連したたんぱく質の異常の探求を通じて、これまで、不明であった変性疾患におけるオートファージー、神経炎症シグナルの異常がALS やアルツハイマー病や多系統萎縮症において示された。シグナル異常が変性疾患の治療対象になる可能性が示唆された。