Molecular pathomechanisms and gene/protein/regeneration therapy for amyotrophic lateral sclerosis

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390267
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Okayama University
• Principal Investigator: ABE Koji 岡山大学, 大学院・医歯薬学総合研究科, 教授 (20212540)
• Co-Investigator(Kenkyū-buntansha): IKEDA Yoshio 岡山大学, 岡山大学病院, 講師 (00282400)
• Project Period (FY): 2009 – 2011
• Keywords: 筋萎縮性側索硬化症 / ALS / SOD1 / neurovascular unit / optineurin / Asidan / SCA36 / NOP56

Research Abstract

To reveal the molecular pathomechanism of amyotrophic lateral sclerosis(ALS), the respective roles of environmental factors such as extracellular matrix, neurovascular unit, or glucose metabolism around spinal motor neurons were investigated in a G93A-SOD1 transgenic mouse model for ALS. The novel responsible genes for familial ALS(optineurin) and the hereditary motor neuron disease(NOP56) had been discovered from this study, and the specific molecular effects of mutated proteins/transcripts were clarified.

Research Products

• [Journal Article] In vivo optical imaging of motor neuron autophagy in a mouse model of amyotrophic lateral sclerosis (2011)
  • Author(s): Tian F, Morimoto N, Liu W, Ohta Y, Deguchi K, Miyazaki K, Abe K
  • Journal Title: Autophagy Volume: 7 Pages: 985-992
  • Peer Reviewed
• [Journal Article] In vivo optical imaging for evaluating the efficacy of edaravone after transient cerebral ischemia inmice (2011)
  • Author(s): Liu N, Shang J, Tian FF, Nishi H, Abe K
  • Journal Title: Brain Res Volume: 1397 Pages: 66-75
  • Peer Reviewed
• [Journal Article] Strong neurogenesis, angiogenesis, synaptogenesis, and antifibrosis of hepatocyte growth factor in rats brain after transient middle cerebral artery occlusion (2011)
  • Author(s): Shang J, Deguchi K, Ohta Y, Liu N, Zhang X, Tian F, Yamashita T, Ikeda Y, Matsuura T, Funakoshi H, Nakamura T, Abe K
  • Journal Title: J Neurosci Res Volume: 89 Pages: 86-95
  • Peer Reviewed
• [Journal Article] Expression of Keap1-Nrf2 system and antioxidative proteins in mouse brain after transient middle cerebral artery occlusion (2011)
  • Author(s): Tanaka N, Ikeda Y, Ohta Y, Deguchi K, Tian F, Shang J, Matsuura T, Abe K
  • Journal Title: Brain Res Volume: 1370 Pages: 246-253
  • Peer Reviewed
• [Journal Article] Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes a type of spinocerebellar ataxia(SCA36) accompanied by motor neuron involvement (2011)
  • Author(s): Kobayashi H, Abe K, Matsuura T, Ikeda Y, Hitomi T, Akechi Y, Habu T, Yang LW, Okuda H, Koizumi A
  • Journal Title: Am J Hum Genet Volume: 89 Pages: 121-130
  • Peer Reviewed
• [Journal Article] Atorvastatin and pitavastatin protect cerebellar Purkinje cells in AD model mice and preserve the cytokines MCP-1 and TNF-α (2011)
  • Author(s): Kozuki M, Kurata T, Miyazaki K, Morimoto N, Ohta Y, Ikeda Y, Abe K
  • Journal Title: Brain Res Volume: 1388 Pages: 32-38
  • Peer Reviewed
• [Journal Article] Progressive neurovascular disturbances in the cerebral cortex of Alzheimer's disease-model mice : protection by atorvastatin and pitavastatin (2011)
  • Author(s): Kurata T, Miyazaki K, Kozuki M, Morimoto N, Ohta Y, Ikeda Y, Abe K
  • Journal Title: Neuroscience Volume: 197 Pages: 358-368
  • Peer Reviewed
• [Journal Article] Atorvastatin and pitavastatin improve cognitive function and reduce senile plaque and phosphorylated tau in aged APP mice (2011)
  • Author(s): Kurata T, Miyazaki K, Kozuki M, Panin VL, Morimoto N, Ohta Y, Nagai M, Ikeda Y, Matsuura T, Abe K
  • Journal Title: Brain Res Volume: 1371 Pages: 161-170
  • Peer Reviewed
• [Journal Article] Early and progressive impairment of spinal blood flow-glucose metabolism coupling in motor neuron degeneration of ALS model mice autophagy in transgenic mice with a G93A mutant SOD1 gene (2011)
  • Author(s): Miyazaki K, Masamoto K, Morimoto N, Kurata T, Mimoto T, Obata T, Kanno I, Abe K
  • Journal Title: J Cereb Blood Flow Metab Volume: 32 Pages: 456-467
  • Peer Reviewed
• [Journal Article] Disruption of neurovascular unit prior to motor neuron degeneration in amyotrophic lateral sclerosis (2011)
  • Author(s): Miyazaki K, Ohta Y, Nagai M, Morimoto N, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Abe K
  • Journal Title: J Neurosci Res Volume: 89 Pages: 718-728
  • Peer Reviewed
• [Journal Article] Correlation of cerebral spinal fluid pH and HCO3-with disease progression in ALS (2011)
  • Author(s): Morimoto N, Nagai M, Ohta Y, Miyazaki K, Kurata T, Morimoto M, Murakami T, Takehisa Y, Ikeda Y, Kamiya T, and Abe K
  • Journal Title: J Neurol Sci Volume: 37 Pages: 74-78
  • Peer Reviewed
• [Journal Article] In Vivo Imaging of Autophagy in a Mouse Stroke Model (2010)
  • Author(s): Tian F, Deguchi K, Yamashita T, Ohta Y, Morimoto N, Shang J, Zhang X, Liu N, Ikeda Y, Matsuura T, and Abe K
  • Journal Title: Autophagy Volume: 6 Pages: 1107-1114
  • Peer Reviewed
• [Journal Article] Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain (2010)
  • Author(s): Kawai H, Yamashita T, Ohta Y, Deguchi K, Nagotani S, Zhang X, Ikeda Y, Matsuura T, and Abe K
  • Journal Title: J Cerebral Blood Flow & Metabolism Volume: 30 Pages: 1487-1493
  • Peer Reviewed
• [Journal Article] In vivo optical imaging of early-stage apoptosis in mouse brain after transient cerebral ischemia (2010)
  • Author(s): Liu N, Deguchi K, Shang J, Zhang X, Tian F, Yamashita T, Ohta Y, Ikeda Y, Matsuura T, Abe K
  • Journal Title: J Neurosci Res Volume: 88 Pages: 3488-3497
  • Peer Reviewed
• [Journal Article] Mutations of optineurin in amyotrophic lateral sclerosis (2010)
  • Author(s): Maruyama H, Morino H, Ito H, Izumi Y, Kato H, Watanabe Y, Kinoshita Y, Kamada M, Nodera H, Suzuki H, Komure O, Matsuura S, Kobatake K, Morimoto N, Abe K, Kawakami H, et al
  • Journal Title: Nature Volume: 465 Pages: 223-226
  • Peer Reviewed
• [Journal Article] Induction of parkinsonism-related proteins in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene (2010)
  • Author(s): Morimoto N, Nagai M, Miyazaki K, Ohta Y, Kurata T, Takehisa Y, Ikeda Y, Matsuura T, Asanuma M and Abe K
  • Journal Title: J Neurosci Res Volume: 88 Pages: 1804-1811
  • Peer Reviewed
• [Journal Article] Antiapoptotic and antiautophagic effects of glial cell line-derived neurotrophic factor and hepatocyte growth factor after transient middle cerebral artery occlusion in rats (2010)
  • Author(s): Shang J, Deguchi K, Yamashita T, Ohta Y, Zhang H, Morimoto N, Liu N, Zhang X, Tian F, Matsuura T, Funakoshi H, Nakamura T and Abe K
  • Journal Title: J Neurosci Res Volume: 88 Pages: 2197-2206
  • Peer Reviewed
• [Journal Article] Temporal and spatial differences of multiple protein expression in the ischemic penumbra after transient MCAO in rats (2010)
  • Author(s): Zhang X, Deguchi K, Yamashita T, Ohta Y, Shang J, Tian F, Liu N, Panin VL, Ikeda Y, Matsuura T, Abe K
  • Journal Title: Brain Res Volume: 1343 Pages: 143-152
  • Peer Reviewed
• [Presentation] In Vivo Optical Imaging for Evaluating the Efficacy of Edaravone after Transient Cerebral Ischemia inMice (2011)
  • Author(s): Liu N, Shang J, Tian FF, Nishi H, Abe K
  • Organizer: 第23回日本脳循環代謝学会総会
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 20111104-05
• [Presentation] In vivo imaging of autophagy after cerebral ischemia in mice (2011)
  • Author(s): Kono S, Tian F, Deguchi K, Yamashita T, and Abe K
  • Organizer: The 5th Japanese-Korean Joint Stroke Conference
  • Place of Presentation: Gyeongju, Korea
  • Year and Date: 20111028-30
• [Presentation] Atorvastatin and pitavastatin reduce senile plaques and inflammatory responses in model mice with Alzheimer's disease (2011)
  • Author(s): Kurata T, Miyazaki K, Kozuki M, Morimoto N, Ohta Y, Abe K
  • Organizer: VASCog 2011
  • Place of Presentation: Lille, France
  • Year and Date: 20110911-14
• [Presentation] Disruption of neurovascular unit relating to oxidative stress and mitochondrial deficit prior to motor neuron degeneration in ALS (2011)
  • Author(s): Miyazaki K, Ohta Y, Morimoto N, Kurata T, Ikeda Y, Matsuura T, Abe K
  • Organizer: The 5th Biennial Meeting of Society for Free Radical Research-Asia
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 20110831-0904
• [Presentation] PROTECTIVE EFFECT OF MITOCHONDRIAL TRANSCROPTION FACTOR A OVEREXPRESSION IN ALS MODEL MICE (2011)
  • Author(s): Morimoto N, Miyazaki K, Kurata T, Ide T, Ikeda Y, Matsuura T, Abe K
  • Organizer: The 5th Biennial Meeting of Society for Free Radical Research-Asia
  • Place of Presentation: Kagoshima, Japan
  • Year and Date: 20110831-0904
• [Presentation] In vivo optical imaging of early stage apoptosis in mice brain after transient cerebral ischemia (2011)
  • Author(s): Liu N, Deguchi K, Shang J, Zhang X, Tian FF, Yamashita T, Ohta Y, Ikeda Y, Matsuura T, Abe K
  • Organizer: 第36回日本脳卒中学会総会
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20110730-0801
• [Presentation] Induction of alpha-synuclein, PINK1, DJ-1 in the spinal motor neurons of transgenic mouse carrying a mutant SOD1 gene (2010)
  • Author(s): Morimoto N, Miyazaki K, Kurata T, Ikeda Y, Matsuura T, Abe K
  • Organizer: 7th Annual Meeting of ASMRM and 10th J-mit
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20101216-18
• [Presentation] Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain (2010)
  • Author(s): Kawai H, Yamashita T, Ohta Y, Deguchi K, Nagotani S, Zhang X, Ikeda Y, Matsuura T, and Abe K
  • Organizer: The 1st World Forum on Cerebral Blood Flow Metabolism & Function
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20101018-20
• [Presentation] Temporal and spatial differences of multiple protein expression in the ischemic penumbra after transient MCAO in rats (2010)
  • Author(s): Zhang X, Deguchi K, Yamashita T, Ohta Y, Shang J, Tian F, Liu N, Panin VL, Ikeda Y, Matsuura T, Abe K
  • Organizer: The 1st World Forum on Cerebral Blood Flow Metabolism & Function
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 20101018-20
• [Presentation] Effect of a free radical scavenger, edaravone, on motor palsy of acute lacunar infarction (2010)
  • Author(s): Omote Y, Ohta Y, Fukushima T, Takamatsu K, Ota T, Goto K, and Abe K
  • Organizer: 6th International Symposium on NEUROPROTECTION AND NEUROREPAIR 2010
  • Place of Presentation: Rostock, Germany
  • Year and Date: 20101001-04
• [Remarks] 岡山大学神経内科ホームページ
  • URL: http://www.okayama-u.ac.jp/user/med/shinkeinaika