Department of Medical Biosciences, Pathology, Umeå University, SE-901 85, Umeå, Sweden.
Acta Neuropathol. 2011 May;121(5):623-34. doi: 10.1007/s00401-011-0805-3. Epub 2011 Feb 3.
The most common cause of amyotrophic lateral sclerosis (ALS) is mutations in superoxide dismutase-1 (SOD1). Since there is evidence for the involvement of non-neuronal cells in ALS, we searched for signs of SOD1 abnormalities focusing on glia. Spinal cords from nine ALS patients carrying SOD1 mutations, 51 patients with sporadic or familial ALS who lacked such mutations, and 46 controls were examined by immunohistochemistry. A set of anti-peptide antibodies with specificity for misfolded SOD1 species was used. Misfolded SOD1 in the form of granular aggregates was regularly detected in the nuclei of ventral horn astrocytes, microglia, and oligodendrocytes in ALS patients carrying or lacking SOD1 mutations. There was negligible staining in neurodegenerative and non-neurological controls. Misfolded SOD1 appeared occasionally also in nuclei of motoneurons of ALS patients. The results suggest that misfolded SOD1 present in glial and motoneuron nuclei may generally be involved in ALS pathogenesis.
肌萎缩侧索硬化症（ALS）最常见的病因是超氧化物歧化酶 1（SOD1）的突变。由于有证据表明非神经元细胞参与了 ALS，我们针对神经胶质细胞寻找 SOD1 异常的迹象。通过免疫组织化学方法检查了 9 名携带 SOD1 突变的 ALS 患者、51 名无此类突变的散发性或家族性 ALS 患者和 46 名对照者的脊髓。使用了一组针对错误折叠 SOD1 物种的特异性抗肽抗体。在携带或不携带 SOD1 突变的 ALS 患者的脊髓前角星形胶质细胞、小胶质细胞和少突胶质细胞的核中，通常可以检测到颗粒状聚集的错误折叠 SOD1。在神经退行性和非神经学对照中，染色可忽略不计。错误折叠的 SOD1 偶尔也出现在 ALS 患者的运动神经元核中。结果表明，存在于神经胶质细胞和运动神经元核中的错误折叠 SOD1 可能普遍参与 ALS 的发病机制。
