2011 Fiscal Year Final Research Report
Role of NUB1 in inclusion body formation in synucleinopathies
| Project/Area Number |
20300123
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TANJI Kunikazu 弘前大学, 大学院・医学研究科, 助教 (10271800)
MORI Fumiaki 弘前大学, 大学院・医学研究科, 准教授 (60200383)
ODAGIRI Saori 弘前大学, 大学院・医学研究科, 助手 (80374817)
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| Project Period (FY) |
2008 – 2011
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| Keywords | 神経変性疾患 / パーキンソン病 / レビー小体型認知症 |
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| Research Abstract |
In human Lewy body disease (LBD), PK-resistant α-synuclein was deposited in Lewy bodies and Lewy neurites, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Biochemical analysis revealed that PK-resistant α-synuclein was detected in the presynaptic fraction in Tg mice and human LBD. We further demonstrated that, in the brains of patients with LBD, NUB1 accumulates in the presynapses in the hippocampus, cerebral neocortex, and substantia nigra in which PK-resistant α-synuclein is deposited. Endogenous NUB1 also accumulated with PK-resistant α-synuclein in the presynapses of Tg mice that express human α-synuclein with an A53T mutation. Immunoelectron microscopy showed that NUB1 was localized to presynaptic nerve terminals where no abnormal filaments were seen. Biochemical analyses showed that NUB1 coexists with abnormal α-synuclein in the brains of LBD patients. These findings suggest that NUB1 along with abnormal α-synuclein is involved in the pathogenesis of LBD.
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