Strengthening mechanism of neuronal vitality by necdin

• Project/Area Number: 24300134
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Osaka University
• Principal Investigator: YOSHIKAWA Kazuaki 大阪大学, たんぱく質研究所, 教授 (30094452)
• Co-Investigator(Kenkyū-buntansha): HASEGAWA Koichi 大阪大学, 蛋白質研究所, 助教 (20546783) ; FUJIWARA Kazushiro 大阪大学, 蛋白質研究所, 助教 (80638495)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Haruki 大阪大学, 蛋白質研究所, 教授 (80134485) ; MOCHIZUKI Hideki 大阪大学, 医学部, 教授 (90230044)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: Necdin / ニューロン / エネルギー代謝 / 生存能 / ミトコンドリア / 神経変性疾患 / PGC-1α / 遺伝子変異マウス / パーキンソン病モデル / 遺伝子導入 / ユビキチン化 / パーキンソン病 / 転写因子 / 活性酸素種 / 酸化ストレス / 翻訳後修飾 / SUMO化 / 立体構造予測

Outline of Final Research Achievements

Necdin promoted mitochondrial biogenesis via stabilization of transcriptional co-activator PGC-1α in neurons and suppressed their degeneration induced by mitochondrial electron transport chain enzyme complex inhibitors. Necdin gene transfer into the substantia nigra in vivo of adult mice prevented mitochondrial complex I inhibitor-induced degeneration of dopaminergic neurons. These results revealed that necdin promotes mitochondrial biogenesis and function in neurons to strengthen their vitality.

Research Products

• [Int'l Joint Research] コロンビア大学(米国)
• [Journal Article] Necdin controls EGFR signaling linked to astrocyte differentiation in primary cortical progenitor cells. (2016)
  • Author(s): Fujimoto, I., Hasegawa, K., Fujiwara, K., Yamada, M., Yoshikawa, K.
  • Journal Title: Cellular Signalling Volume: 28 Issue: 2 Pages: 94-107
  • DOI: 10.1016/j.cellsig.2015.11.016
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults. (2016)
  • Author(s): Hasegawa, K., Yasuda, T., Shiraishi, C., Fujiwara, K., Przedborski, S., Mochizuki, H., Yoshikawa, K.
  • Journal Title: Nature Communications Volume: 7 Issue: 1 Pages: 10943-10943
  • DOI: 10.1038/ncomms10943
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Antagonistic interplay between necdin and Bmi1 controls proliferation of neural precursor cells in the embryonic mouse neocortex (2014)
  • Author(s): Minamide, R., Fujiwara, K., Hasegawa, K., Yoshikawa, K.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e84460-e84460
  • DOI: 10.1371/journal.pone.0084460
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Necdin promotes ubiquitin-dependent degradation of PIAS1 SUMO E3 ligase (2014)
  • Author(s): Gur, I., Fujiwara, K., Hasegawa, K., Yoshikawa, K.
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e99503-e99503
  • DOI: 10.1371/journal.pone.0099503
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Necdin controls proliferation and apoptosis of embryonic neural stem cells in an oxygen tension-dependent manner (2013)
  • Author(s): Huang, Z., Fujiwara, K., Minamide, R., Hasegawa, K., Yoshikawa, K.
  • Journal Title: Journal of Neuroscience Volume: 33 Issue: 25 Pages: 10362-10373
  • DOI: 10.1523/jneurosci.5682-12.2013
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Non-epithelial stem cells and cortical interneuron production in the human ganglionic eminences (2013)
  • Author(s): Hansen, D., Lui, J., Flandin, P., Yoshikawa, K., Rubenstein, J., Alvarez-Buylla, A., Kriegstein, A.
  • Journal Title: Nature Neuroscience Volume: 16 Issue: 11 Pages: 1576-1587
  • DOI: 10.1038/nn.3541
  • Peer Reviewed
• [Journal Article] Early decline in progenitor diversity in the marmoset lateral ventricle (2013)
  • Author(s): Azim, K., Zweifel, S., Klaus, F., Yoshikawa, K., Amrein, I., Raineteau, O.
  • Journal Title: Cerebral Cortex Volume: 23 Issue: 4 Pages: 922-931
  • DOI: 10.1093/cercor/bhs085
  • Peer Reviewed
• [Journal Article] Necdin controls proliferation of white adipocyte progenitor cells (2012)
  • Author(s): Fujiwara, K., Hasegawa, K., Ohkumo, T., Miyoshi, H., Tseng, Y. H., Yoshikawa, K.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Dynamic expression of the pro-dopaminergic transcription factors Pax6 and Dlx2 during postnatal olfactory bulb neurogenesis (2012)
  • Author(s): de Chevigny, A., Core, N., Follert, P., Wild, S., Bosio, A., Yoshikawa, K., Cremer, H., Beclin, C.
  • Journal Title: Front Cell Neurosci Volume: 6
  • DOI: 10.3389/fncel.2012.00006
  • Peer Reviewed
• [Journal Article] β-Catenin signaling specifies progenitor cell identity in parallel with Shh signaling in the developing mammalian thalamus (2012)
  • Author(s): Bluske, K. K., Vue, T. Y., Kawakami, Y., Taketo, M. M., Yoshikawa, K., Johnson, J. E., Nakagawa, Y.
  • Journal Title: Development Volume: 139 Issue: 15 Pages: 2692-2702
  • DOI: 10.1242/dev.072314
  • Peer Reviewed
• [Journal Article] 3-dimensional examination of the adult mouse subventricular zone reveals lineage-specific microdomains (2012)
  • Author(s): Azim, K., Fiorelli, R., Zweifel, S., Hurtado-Chong, A., Yoshikawa, K., Slomianka, L., Raineteau, O.
  • Journal Title: PLoS One Volume: 7
  • Peer Reviewed
• [Journal Article] Necdin controls Foxol acetylation in hypothalamic arcuate neurons to modulate the thyroid axis (2012)
  • Author(s): Hasegawa, K., Kawahara, T., Fujiwara, K., Shimpuku, M., Sasaki, T., Kitamura, T., Yoshikawa, K.
  • Journal Title: Journal of Neuroscience Volume: 32 Pages: 5562-5572
  • Peer Reviewed
• [Journal Article] Thyroid hormone signaling acts as a neurogenic switch by repressing Sox2 in the adult neural stem cell niche (2012)
  • Author(s): Lopez-Juarez, A., Remaud, S., Hassani, Z., Jolivet, P., Pierre Simons, J., Sontag, T., Yoshikawa, K., Price, J., Morvan-Dubois, G., Demeneix, B. A.
  • Journal Title: Cell Stem Cell Volume: 10 Issue: 5 Pages: 531-543
  • DOI: 10.1016/j.stem.2012.04.008
  • Peer Reviewed
• [Journal Article] BMP receptor 1A regulates development of hypothalamic circuits critical for feeding behavior (2012)
  • Author(s): Peng, C. Y., Mukhopadhyay, A., Jarrett, J. C., Yoshikawa, K., Kessler, J. A.
  • Journal Title: Journal of Neuroscience Volume: 32 Issue: 48 Pages: 17211-17224
  • DOI: 10.1523/jneurosci.2484-12.2012
  • Peer Reviewed
• [Journal Article] ERK inhibition rescues defects in fate specification of Nf1 -deficient neural progenitors and brain abnormalities (2012)
  • Author(s): Wang, Y., Kim, E., Wang, X. Novitch, B. G., Yoshikawa, K., Chang, L. S., Zhu, Y.
  • Journal Title: Cell Volume: 150 Issue: 4 Pages: 816-830
  • DOI: 10.1016/j.cell.2012.06.034
  • Peer Reviewed
• [Presentation] ニューロン分化におけるNecdinによるRanGAP1のSUMO化制御 (2015)
  • Author(s): 藤原一志郎, 長谷川孝一, 吉川和明
  • Organizer: 第88回 日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市）
  • Year and Date: 2015-12-03
• [Presentation] 神経前駆細胞におけるNecdinによる上皮成長因子受容体シグナルの制御機構 (2015)
  • Author(s): 藤本泉, 長谷川孝一, 藤原一志郎, 吉川和明
  • Organizer: 第88回 日本生化学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Necdin promotes mitochondrial biogenesis to prevent neurodegeneration in experimental Parkinson's disease (2015)
  • Author(s): Hasegawa K, Yasuda T, Shiraishi C, Fujiwara K, Mochizuki H, Yoshikawa K
  • Organizer: Neuroscience 2015, Society for Neuroscience
  • Place of Presentation: Chicago（USA)
  • Year and Date: 2015-10-21
  • Int'l Joint Research
• [Presentation] Necdin downregulates EGFR signaling in cortical neural precursor cells to suppress gliogenesis (2015)
  • Author(s): Fujimoto I, Hasegawa K, Fujiwara K, Yoshikawa K
  • Organizer: Neuroscience 2015, ociety for Neuroscience
  • Place of Presentation: Chicago（USA)
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Promotion of neuronal mitochondiral biogenesis by necdin: Neuroprotection in experimental Parkinsonism (2015)
  • Author(s): 吉川和明, 長谷川孝一, 安田徹, 望月秀樹
  • Organizer: 第３８回 日本神経科学会大会
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市）
  • Year and Date: 2015-07-29
  • Invited
• [Presentation] Necdin regulates RanGAP1 sumoylation during neuronal differentiation (2014)
  • Author(s): Fujiwara, K., Hasegawa, K., Yoshikawa, K.
  • Organizer: Neuroscience 2014
  • Place of Presentation: Walter E. Washington Convention Center, Washington D.C.
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Necdinによる上皮成長因子受容体シグナルの制御機構 (2014)
  • Author(s): 藤本泉、 長谷川孝一、 藤原一志郎、 吉川和明
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館 (京都市)
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] Necdinによるニューロン内ミトコンドリア機能の促進：パーキンソン病モデルにおける神経保護作用 (2014)
  • Author(s): 長谷川孝一、安田徹、白石千夏、藤原一志郎、望月秀樹、吉川和明
  • Organizer: 第57回日本神経化学会大会
  • Place of Presentation: 奈良県文化会館 (奈良市)
  • Year and Date: 2014-09-29 – 2014-10-01
• [Presentation] NecdinによるPGC-1αを介したニューロン内ミトコンドリア機能の促進 (2013)
  • Author(s): 長谷川孝一、白石千夏、藤原 一志郎 吉川 和明
  • Organizer: 第８6回日本生化学会大会
  • Place of Presentation: パシフィコ横浜 (横浜市）
  • Year and Date: 2013-09-11 – 2013-09-13
• [Presentation] Necdin suppresses PIAS1 SUMO E3 ligase activity by promoting ubiquitin-dependent degradation (2013)
  • Author(s): GUR Ibrahim、藤原一志郎、長谷川孝一、吉川和明
  • Organizer: 第８6回日本生化学会大会
  • Place of Presentation: パシフィコ横浜 (横浜市）
  • Year and Date: 2013-09-11 – 2013-09-13
• [Presentation] NecdinによるRanGAP1のSUMO化制御 (2013)
  • Author(s): 藤原一志郎、長谷川孝一、吉川和明
  • Organizer: 第８6回日本生化学会大会
  • Place of Presentation: パシフィコ横浜 (横浜市）
  • Year and Date: 2013-09-11 – 2013-09-13
• [Presentation] NecdinによるPGC-1αの安定化を介したニューロン内ミトコンドリア生合成の促進 (2013)
  • Author(s): 長谷川孝一、白石千夏、藤原一志郎、吉川和明
  • Organizer: 第56回日本神経化学会大会
  • Place of Presentation: 国立京都国際会館 (京都市）
  • Year and Date: 2013-06-20 – 2013-06-23
• [Presentation] NecdinとBmi1の拮抗的相互作用による神経幹細胞の増殖制御 (2013)
  • Author(s): 南出良平、長谷川孝一、藤原一志郎 吉川和明
  • Organizer: 第56回日本神経化学会大会
  • Place of Presentation: 国立京都国際会館 (京都市）
  • Year and Date: 2013-06-20 – 2013-06-23
• [Presentation] In vitro SUMO化反応系によるNecdinのSUMO修飾解析 (2012)
  • Author(s): 藤原一志郎、長谷川孝一、江連徹、吉川和明
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(招待講演)
  • Year and Date: 2012-12-15
• [Presentation] NecdinによるPGC-1αを介したニューロン内ミトコンドリア生合成の促進 (2012)
  • Author(s): 長谷川孝一、白石千夏、藤原一志郎、吉川和明
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(招待講演)
  • Year and Date: 2012-12-15
• [Presentation] 哺乳類ニューロンのDNA修復におけるNecdinの関与 (2012)
  • Author(s): 瀬戸口良、長谷川孝一、三津昭博、吉川和明
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(招待講演)
  • Year and Date: 2012-12-15
• [Remarks] 大阪大学蛋白質研究所神経発生制御研究室ホームページ
  • URL: http://www.protein.osaka-u.ac.jp/regulation/index_jap.html
• [Remarks]
  • URL: http://www.protein.osaka-u.ac.jp/regulation