Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study.
Mitochondrial abnormalities and low grade inflammation are present in the skeletal muscle of a minority of patients with amyotrophic lateral sclerosis; an observational myopathology study.
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DOI：
10.1186/s40478-014-0165-z
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发表时间：
2014-12-14
影响因子：
7.1
通讯作者：
Meininger V
中科院分区：
文献类型：
--
作者：
Al-Sarraj S;King A;Cleveland M;Pradat PF;Corse A;Rothstein JD;Leigh PN;Abila B;Bates S;Wurthner J;Meininger V
肌萎缩侧索硬化症(ALS)是一种以下运动神经元(脊髓和脑干)和/或上运动神经元(运动皮质)神经元丢失为特征的原发进行性神经退行性疾病，随后骨骼肌失神经萎缩。对一组临床确诊的肌萎缩侧索硬化症患者的肌肉病理进行的全面检查，包括对炎症、补体激活和异常蛋白沉积的调查，以便将它们与年龄匹配的对照组的结果进行比较。对31例临床确诊的ALS患者和20例正常对照的肌肉活检进行了全面的组织化学和免疫组织化学染色，包括人类白细胞抗原-ABC、C5b-9、p62和TDP-43。31例肌萎缩侧索硬化症患者中30例有神经源性改变。在一例中，没有检测到神经源性变化。肌纤维坏死5例，慢性单核细胞炎性细胞浸润5/31例(其中2例与肌肉坏死重叠)。在4例活检组织中，细胞色素氧化酶(COX)阴性纤维的比例增加(2-3%)。8例P62胞浆呈微弱染色，无TDP-43免疫反应阳性。来自ALS患者的大量肌肉活组织检查表明，神经源性萎缩几乎是一致的发现，可以看到轻微的线粒体异常和低度炎症，不排除ALS的诊断。这些发现可能支持肌萎缩侧索硬化症是一种复杂和异质性疾病的观点。
Amyotrophic lateral sclerosis (ALS) is a primary progressive neurodegenerative disease characterised by neuronal loss of lower motor neurons (in the spinal cord and brainstem) and/or upper motor neurons (in the motor cortex) and subsequent denervation atrophy of skeletal muscle. A comprehensive examination of muscle pathology from a cohort of clinically confirmed ALS patients, including an investigation of inflammation, complement activation, and deposition of abnormal proteins in order to compare them with findings from an age-matched, control group. 31 muscle biopsies from clinically confirmed ALS patients and 20 normal controls underwent a comprehensive protocol of histochemical and immunohistochemical stains, including HLA-ABC, C5b-9, p62, and TDP-43. Neurogenic changes were confirmed in 30/31 ALS cases. In one case, no neurogenic changes could be detected. Muscle fibre necrosis was seen in 5/31 cases and chronic mononuclear inflammatory cell infiltration in 5/31 (2 of them overlapped with those showing muscle necrosis). In four biopsies there was an increase in the proportion of cytochrome oxidase (COX) negative fibres (2-3%). p62 faintly stained cytoplasmic bodies in eight cases and none were immunoreactive to TDP-43. This large series of muscle biopsies from patients with ALS demonstrates neurogenic atrophy is a nearly uniform finding and that mild mitochondrial abnormalities and low-grade inflammation can be seen and do not rule out the diagnosis of ALS. These findings could lend support to the notion that ALS is a complex and heterogeneous disorder.
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影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
影响因子：
2.2
作者：
Finsterer, J
通讯作者：
Finsterer, J
影响因子：
11.2
作者：
Comi, GP;Bordoni, A;Scarlato, G
通讯作者：
Scarlato, G
影响因子：
11.2
作者：
Brierley, EJ;Johnson, MA;Turnbull, DM
通讯作者：
Turnbull, DM
DOI：
10.1073/pnas.0605814103
发表时间：
2006-09-12
影响因子：
11.1
作者：
Ferri, Alberto;Cozzolino, Mauro;Carri, Maria Teresa
通讯作者：
Carri, Maria Teresa