Elucidating the molecular pathology of neurodegenerative diseases through analysis of the aggregate-binding protein SGTA

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15731
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Yokohama City University
• Principal Investigator: KUBOTA Shun 横浜市立大学, 附属病院, 助教 (60891851)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 神経変性疾患 / タンパク質凝集体

Outline of Final Research Achievements

We assessed the relationship between the aggregate binding protein SGTA and protein aggregates related to neurodegenerative diseases. We overexpressed aggregate-related protein associated with various neurodegenerative diseases in the Neuro2A cell line and induced the formation of intracellular aggregates. First, we overexpressedα-synuclein, a protein that forms glial cytoplasmic inclusions in multiple system atrophy. We induced the formation of aggregates of wild-type α-synuclein or disease-related variant(A53T) α-synuclein. We performed the immunocytochemistry to assess the co-localization of SGTA and α-synuclein aggregates. It was not observed that co-localization of SGTA and α-synuclein aggregates. Next, we overexpressed TDP43 or UBQLN2, which are components of the inclusion bodies found in the neural tissue of ALS. It was observed that forming TDP43 aggregates or UBQLN2 aggregates in Neuro2A. There is no observed co-localization of SGTA with either TDP43 or UBQLN2 aggregates.

Free Research Field

神経変性疾患

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患は慢性進行性に神経細胞が変性, 脱落し神経症状を呈する神経難病の総称である. 代表的な疾患としてアルツハイマー病, パーキンソン病, ALSやポリグルタミン病などがあり,いずれも根治療法はない. 多くの神経変性疾患でみられる共通の特徴として神経組織へのタンパク質凝集体の沈着があり凝集体形成は神経変性疾患に共通した分子病態に関与すると考えられる. 凝集体結合タンパク質の病態への関与を解明する事は神経変性疾患全般の治療開発において重要な意義を有する.本研究では申請者らが独自に同定した凝集体結合タンパク質であるSGTAに着目し各種神経変性疾患でみられるタンパク質凝集体との関連を検討した.