Fungal infection in neural tissue of patients with amyotrophic lateral sclerosis
Fungal infection in neural tissue of patients with amyotrophic lateral sclerosis
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DOI：
10.1016/j.nbd.2017.09.001
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发表时间：
2017-12-01
影响因子：
6.1
通讯作者：
Carrasco, Luis
中科院分区：
文献类型：
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作者：
Alonso, Ruth;Pisa, Diana;Carrasco, Luis
肌萎缩侧索硬化症（ALS）是一种破坏性的神经退行性疾病，也是运动神经元病理的主要原因。该疾病的病因仍不清楚，并且没有有效的疗法可以阻止该疾病或改善生活质量。在这里，我们为 ALS 中存在真菌感染提供了令人信服的证据。使用一组抗真菌抗体进行的免疫组织化学分析揭示了 11 名 ALS 患者的运动皮层、髓质和脊髓中存在酵母和菌丝等真菌结构。一些真菌结构位于细胞内甚至核内，表明这种感染不是死后定植的结果。相比之下，在对照受试者的几个中枢神经系统区域中无法观察到这种真菌感染负担。对从冷冻神经组织中提取的 DNA 进行 PCR 分析和新一代测序，鉴定出多种真菌属，包括念珠菌属、马拉色菌属、镰刀菌属、Bottytis 属、木霉属和隐球菌属。总体而言，我们目前的观察结果为 ALS 患者存在混合真菌感染提供了强有力的证据。确切的混合感染因患者而异，这与每个 ALS 患者症状的不同演变和严重程度一致。这些新发现为这种疾病的神经病理学观察结果（例如神经炎症和几丁质酶水平升高）提供了逻辑解释，并有助于实施适当的治疗。
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and the main cause of motor neuron pathology. The etiology of the disease remains unknown, and no effective therapy exists to halt the disease or improve the quality of life. Here, we provide compelling evidence for the existence of fungal infection in ALS. Immunohistochemistry analysis using a battery of antifungal antibodies revealed fungal structures such as yeast and hyphae in the motor cortex, the medulla and the spinal cord, in eleven patients with ALS. Some fungal structures were localized intracellularly and even intranuclearly, indicating that this infection is not the result of post-mortem colonization. By contrast, this burden of fungal infection cannot be observed in several CNS areas of control subjects. PCR analysis and next generation sequencing of DNA extracted from frozen neural tissue identified a variety of fungal genera including Candida, Malassezia, Fusarium, Bottytis, Trichoderma and Cryptococcus. Overall, our present observations provide strong evidence for mixed fungal infections in ALS patients. The exact mixed infection varies from patient to patient consistent with the different evolution and severity of symptoms in each ALS patient. These novel findings provide a logical explanation for the neuropathological observations of this disease, such as neuroinflammation and elevated chitinase levels, and could help to implement appropriate therapies.