Elevated levels of amyloid precursor protein in muscle of patients with amyotrophic lateral sclerosis and a mouse model of the disease
Elevated levels of amyloid precursor protein in muscle of patients with amyotrophic lateral sclerosis and a mouse model of the disease
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DOI：
10.1002/mus.20612
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发表时间：
2006-10-01
期刊：
影响因子：
3.4
通讯作者：
Dingwall, Colin
中科院分区：
文献类型：
--
作者：
Koistinen, Hannu;Prinjha, Rab;Dingwall, Colin
肌萎缩侧索硬化症 (ALS) 是一种进行性神经退行性疾病，定义为运动神经元损失。转基因小鼠模型显示出的特征与临床情况非常相似，反映在小鼠模型和患者组织中观察到的分子变化中。我们报告称，G93A 转基因小鼠模型的后肢肌肉中淀粉样前体蛋白 (APP) 的表达显着增加，但脊髓中的淀粉样蛋白前体蛋白的表达并未显着增加，明显早于临床异常的出现。在非转基因小鼠和过表达人野生型 Cu/Zn 依赖性超氧化物歧化酶 1 (SOD1) 的小鼠中，APP 水平没有变化。初步结果表明，与年龄匹配的对照相比，ALS 患者的人类三角肌样本中 APP 表达发生了类似的变化。 APP 在神经肌肉接头神经支配中的抑制作用以及包涵体肌炎中表达的增加表明 APP 症状前上调可能与 APP 在 ALS 病理学中的潜在作用一致。
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease defined by motor neuron loss. Transgenic mouse models show features that closely mimic those seen in the clinical situation, reflected in the molecular changes observed in mouse models and in tissues from patients. We report a dramatic increase in the expression of amyloid precursor protein (APP) in the hindlimb muscles, but not the spinal cord of the G93A transgenic mouse model, significantly before the appearance of clinical abnormalities. APP levels were unchanged in nontransgenic mice and in mice overexpressing human wild-type Cu/Zn-dependent superoxide dismutase 1 (SOD1). Preliminary results indicate a similar change in APP expression in human deltoid muscle samples from ALS patients compared with age-matched controls. The inhibitory role of APP in innervation at the neuromuscular junction and increased expression in inclusion-body myositis suggest that presymptomatic upregulation of APP may be consistent with a potential role for APP in ALS pathology.