Elucidation of mechanisms of prionoid conversion of alpha-synuclein by imaging mass spectrometry
| Project/Area Number |
17K19658
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
General internal medicine and related fields
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
Nagai Yoshitaka 大阪大学, 医学系研究科, 寄附講座教授 (60335354)
|
|---|
| Project Period (FY) |
2017-06-30 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2017: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
|
|---|
| Keywords | 脳神経疾患 / 蛋白質 / 脂質 / 分析科学 / 質量顕微鏡 / ショウジョウバエ / 質量分析顕微鏡 |
|---|
| Outline of Final Research Achievements |
In this study, we investigated the role of lipids on prionoid conversion and aggregation of α-synuclein (αSyn) in Parkinson’s disease and other synucleinopathies. We performed mass spectrometry imaging analyses of patients’ brains and identified some lipids that promote prionoid conversion of αSyn. We also established novel reporter flies for αSyn transmission in the brain.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は、異なるバックグランドの研究者の協力を得て、質量分析イメージングなど最先端の物理化学的技術の医学・生物学への導入を促進するという点で、挑戦的研究としての意義が高い。本研究により、蛋白質プリオノイド化の誘因として脂質の役割りが明らかになり、その構造多様性が疾患多様性を引き起こすメカニズムは、アルツハイマー病や前頭側頭型認知症など他の神経変性疾患にも共通する可能性がある。
|
Report
(4 results)
Research Products
(115 results)
-
-
-
-
[Journal Article] Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.2019
Author(s)
2. Kakuda K, Ikenaka K, Araki K, So M, Aguirre C, Kajiyama Y, Konaka K, Noi K, Baba K, Tsuda H, Nagano S, Ohmichi T, Nagai Y, Tokuda T, El-Agnaf O, Ogi H, Goto Y, Mochizuki H.
-
Journal Title
Sci Rep
Volume: 9
Issue: 1
Pages: 6001-6001
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
[Journal Article] Arylsulfatase A, a genetic modifier of Parkinson's disease, is an α-synuclein chaperone.2019
Author(s)
J. S. Lee, K. Kanai, M. Suzuki, W. S. Kim, H. S. Yoo, Y. Fu, D-K. Kim, B. C. Jung, M. Choi, K. W. Oh, Y. Li, M. Nakatani, T. Nakazato, S. Sekimoto, M. Furuyama, H. Yoshino, S. Kubo, K. Nishioka, R. Sakai, M. Ueyama, H. Mochizuki, H-J. Lee, S. P. Sardi, G. M. Halliday, Y. Nagai, P. H. Lee, N. Hattori, S-J. Lee
-
Journal Title
Brain
Volume: 142
Issue: 9
Pages: 2845-59
DOI
Related Report
Peer Reviewed / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced by knockdown of Caz, Drosophila FUS.2018
Author(s)
Azuma Y, Tokuda T, Kushimura Y, Yamamoto I, Mizuta I, Mizuno T, Nakagawa M, Ueyama M, Nagai Y, Iwasaki Y, Yoshida M, Pan D, Yoshida H, Yamaguchi M.
-
Journal Title
Exp Cell Res.
Volume: 371
Issue: 2
Pages: 311-321
DOI
Related Report
Peer Reviewed / Open Access
-
-
[Journal Article] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2018
Author(s)
Yoshida S, Hasegawa T, Suzuki M, Sugeno N, Kobayashi J, Ueyama M, Fukuda M, Ido-Fujibayashi A, Sekiguchi K, Ezura M, Kikuchi A, Baba T, Takeda A, Mochizuki H, Nagai Y and Aoki M.
-
Journal Title
Hum Mol Genet.
Volume: 27
Issue: 5
Pages: 823-836
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Overexpression of ter94, Drosophila VCP, improved motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2018
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
-
Journal Title
Am. J. Neurodegener. Dis.
Volume: 1
Pages: 11-31
Related Report
Peer Reviewed
-
[Journal Article] A spontaneously immortalized Schwann cell line from aldose reductase-deficient mice as a useful tool for studying polyol pathway and aldehyde metabolism.2018
Author(s)
2.Niimi N, Yako H, Takaku S, Kato H, Matsumoto T, Nishito Y, Watabe K, Ogasawara S, Mizukami H, Yagihashi S, Chung SK, Sango K.
-
Journal Title
Journal of Neurochemistry
Volume: 印刷中
Pages: 97-106
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Establishment of slowly progressive Parkinson's disease marmoset model by α-synuclein fibril injection.2018
Author(s)
Yabumoto T., Baba K., Hayakawa H., Yoshida F., Uehara T., Nakatani R., Ikenaka K., Tsuda H., Nagano S., Nagai Y., Hamanaka H., Hirata M., Mochizuki H.
Organizer
The 143rd Annual Meeting of the American Neurological Association
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
[Presentation] Regulatory role of RNA chaperone for noncoding repeat RNA aggregation and repeat-associated translation in SCA31.2017
Author(s)
Nagai Y., Ishiguro T., Sato N., Ueyama M., Fujikake N., Yokota T., Wada K., Mizusawa H., Ishikawa K.
Organizer
The 43rd Naito Conference on Noncoding RNA：Biology, Chemistry, & Diseases
Related Report
Int'l Joint Research
-
[Presentation] Transgenic monkey model of the polyglutamine diseases recapitulating progressive neurological symptoms and polyglutamine protein inclusions.2017
Author(s)
Nagai Y., Tomioka I., Ishibashi H., Minakawa E.N, Motohashi H.H., Takayama O., Saito Y., Popiel H.A., Puentes S., Owari K., Nakatani T., Nogami N., Yamamoto K., Noguchi S., Nagano S., Nishino I., Ichinohe N., Wada K., Kohsaka S., Seki K.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
-
-
-
-
-
[Presentation] Balance between RNA binding proetin TDP-43 and an RNA UGGAA repeat underlies pathogenesis of spinocerebellar ataxia type 31 (SCA31) and motor neuron disease fly models.2017
Author(s)
Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y., Ishikawa K.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
-
[Presentation] Parkinson’s disease-linked DNAJC13 mutation aggravates α-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.2017
Author(s)
Hasegawa T., Yoshida S., Suzuki M., Sugeno N., Kobayashi J., Ueyama M., Ezura M., Kikuchi A., Baba T., Takeda A., Mochizuki H., Nagai Y., Aoki M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
-
-
-
-
-
[Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model.2017
Author(s)
Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
-
[Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2017
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Yoshida H., Mizuta I., Ueyama M., Nagai Y., Nakagawa M., Mizuno T., Yamaguchi M.
Organizer
The 23rd World Congress of Neurology (WCN 2017)
Related Report
Int'l Joint Research
-
-
[Presentation] The search for genes that modulate FUS-mediated phenotypes by Drosophila amyotrophic lateral sclerosis model.2017
Author(s)
Azuma Y., Tokuda T., Kushimura Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
Organizer
CSHL 2017 Neurobiology of Drosophila
Related Report
Int'l Joint Research
-
[Presentation] Loss of function mutant of ter94, Drosophila VCP, partially enhanced motor neuron degeneration induced by knockdown of TBPH, Drosophila TDP-43.2017
Author(s)
Kushimura Y., Tokuda T., Azuma Y., Yamamoto I., Ueoka I., Mizuta I., Mizuno T., Nakagawa M., Ueyama M., Nagai Y., Yoshida H., Yamaguchi M.
Organizer
CSHL 2017 Neurobiology of Drosophila
Related Report
Int'l Joint Research
-
[Presentation] Regulatory role of RNA chaperone TDP-43 for RNA misfolding and repeat-associated translation in SCA31.2017
Author(s)
Ishikawa K., Ishiguro T., Sato N., Ueyama M., Fujikake N., Sellier C., Tokuda E., Zamiri B., Gall-Duncan T., Mirceta M., Furukawa Y., Yokota T., Wada K., Taylor J.P., Pearson C.E., Charlet-Berguerand N., Mizusawa H., Nagai Y.
Organizer
67th Annual Meeting of American Society of Human Genetics
Related Report
Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
