Anti-apoptotic Therapy (Intrathecal Injection of Anti-apoptotic PTD-FNK Protein) in a Mouse Model of Amyotrophic Lateral Sclerosis

肌萎缩侧索硬化症小鼠模型的抗凋亡治疗（鞘内注射抗凋亡 PTD-FNK 蛋白）

• 批准号: 17590879
• 负责人: TAKEHISA Yasushi
• 金额: $ 1.98万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590879/
• 关键词: ALS; ant-apoptotic therapy; neural precursor cell; IGF-1; neurotrophic factors; FNK; intrathecal infusion; SODG93A transgenic mice; 抗アポトーシス治療法; 筋萎縮性側索硬化症(ALS)

We investigated three steps of neural precursor cell activation-proliferation, migration, and differentiation.in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide disniutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule.1 (Ibal), BrdU + glial fibrillary acidic protein (GFAP). or BrdU + highly polysialylated neural cell adhesion molecule (.PSA-NCAM.) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns. which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.

我们研究了神经前体细胞激活的三个步骤-增殖、迁移和肌萎缩性侧索硬化脊髓，通过鞘内输注表皮生长因子（EGF）和成纤维细胞生长因子2（FGF2）到正常和有症状的转基因（Tg）小鼠的腰髓区域，这些小鼠具有突变的人铜/锌超氧化物歧化酶（SOD 1）基因。我们观察到，5-溴脱氧尿苷（BrdU）+巢蛋白双标记的神经前体细胞增加，在Tg小鼠的脊髓与非Tg小鼠相比，与EGF和FGF2治疗产生的更大的增加。BrdU + Nestin双标细胞数明显多于BrdU+钙离子结合接头分子1（Ibal）、BrdU+胶质细胞酸性蛋白（GFAP）双标细胞数。或BrdU+高度多聚唾液酸化的神经细胞粘附分子（. PSA-NCAM.）双标记细胞，但没有表达神经元核抗原（NeuN）。进一步分析Tg小鼠的灰质，BrdU + nestin和BrdU + PSA-NCAM双标记细胞的数量在腹角比背角增加更多。EGF和FGF2处理再次大大增强。由于神经前体细胞位于中央管室管膜附近，因此本研究表明，在有症状的Tg小鼠中，神经前体细胞向腹角的增殖和迁移被极大地激活，并且通过EGF和FGF2治疗进一步增强，此外，在EGF和FGF2治疗的Tg小鼠中，神经前体细胞优先分化为神经元前体细胞而不是星形胶质细胞。

项目成果

Therapeutic benefit of intrathecal injection of insulin-like growth factor-1 in a mouse model of Amyotrophic Lateral Sclerosis

• DOI: 10.1016/j.jns.2005.04.011
• 发表时间: 2005-08-15
• 期刊: JOURNAL OF THE NEUROLOGICAL SCIENCES
• 影响因子: 4.4
• 作者: Nagano, I;Ilieva, H;Abe, K
• 通讯作者: Abe, K

PINK1, a gene product of PARK6, accumulates in □-synucleinopathy brains.

PINK1 是 PARK6 的基因产物，在 □-突触核蛋白病大脑中积聚。

• 发表时间: 2007
• 期刊: J Neurol Neurosurg Psychiatry. 8(Epub ahead of prin)
• 作者: Murakami T;Moriwaki Y;Kawarabayashi T;Nagai M;Ohta;Y;Deguchi K;Kurata T;Takehisa Y;Matsubara E;Ikeda M;Harigaya Y;Shoji M;Takahashi R;Abe
• 通讯作者: Abe

Beneficial effects of intrathecal IGF-1 administration inpatients with amyotrophic lateralsclerosis

肌萎缩侧索硬化症患者鞘内注射 IGF-1 的有益效果

• 发表时间: 2006
• 作者: Murakami T;Nagano I;Nagai M;Shiote M;Ohta Y;Morimoto N;Takehisa Y;Kaand Abe K.
• 通讯作者: Kaand Abe K.

Protein-bound crotonaldehyde accumulates in the spinal cord of superoxide dismutase-1 mutation-associated familial amyotrophic lateral sclerosis and its transgenic mouse model

超氧化物歧化酶-1突变相关的家族性肌萎缩侧索硬化症及其转基因小鼠模型脊髓中蛋白质结合的巴豆醛积聚

• 发表时间: 2007
• 期刊: Neuropathology 27
• 作者: Shibata N;Kawaguchi M;Uchida K;Kakita A;Takahashi H;Sasaki S;et.al.
• 通讯作者: et.al.

Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene

• DOI: 10.1002/jnr.21017
• 发表时间: 2006-10
• 期刊: Journal of Neuroscience Research
• 影响因子: 4.2
• 作者: Y. Ohta;M. Nagai;T. Nagata;T. Murakami;I. Nagano;H. Narai;T. Kurata;M. Shiote;M. Shoji;K. Abe