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首页> 外文期刊>The Journal of Clinical Investigation: The Official Journal of the American Society for Clinical Investigation >Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease
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Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease

机译：两种超氧化物歧化酶朊病毒株传播肌萎缩侧索硬化样疾病

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摘要

Amyotrophic lateral sclerosis (ALS) is an adult-onset degeneration of motor neurons that is commonly caused by mutations in the gene encoding superoxide dismutase 1 (SOD1). Both patients and Tg mice expressing mutant human SOD1 (hSOD1) develop aggregates of unknown importance. In Tg mice, 2 different strains of hSOD1 aggregates (denoted A and B) can arise; however, the role of these aggregates in disease pathogenesis has not been fully characterized. Here, minute amounts of strain A and B hSOD1 aggregate seeds that were prepared by centrifugation through a density cushion were inoculated into lumbar spinal cords of 100-day-old mice carrying a human SOD1 Tg. Mice seeded with A or B aggregates developed premature signs of ALS and became terminally ill after approximately 100 days, which is 200 days earlier than for mice that had not been inoculated or were given a control preparation. Concomitantly, exponentially growing strain A and B hSOD1 aggregations propagated rostrally throughout the spinal cord and brainstem. The phenotypes provoked by the A and B strains differed regarding progression rates, distribution, end-stage aggregate levels, and histopathology. Together, our data indicate that the aggregate strains are prions that transmit a templated, spreading aggregation of hSOD1, resulting in a fatal ALS-like disease.
机译：肌萎缩侧索硬化症 （ALS） 是一种成人发病的运动神经元变性，通常由编码超氧化物歧化酶 1 （SOD1） 的基因突变引起。患者和表达突变人SOD1（hSOD1）的Tg小鼠都发育出重要性未知的聚集体。在 Tg 小鼠中，可以出现 2 种不同的 hSOD1 聚集体菌株（表示为 A 和 B）;然而，这些聚集体在疾病发病机制中的作用尚未得到充分表征。在这里，通过密度垫离心制备的微量菌株 A 和 B hSOD1 聚集体种子接种到携带人 SOD1 Tg 的 100 日龄小鼠的腰椎脊髓中。 接种 A 或 B 聚集体的小鼠出现 ALS 的过早迹象，并在大约 100 天后患上绝症，这比未接种或给予对照制剂的小鼠早 200 天。同时，呈指数增长的菌株 A 和 B hSOD1 聚集体在整个脊髓和脑干中喙向传播。A株和B株引起的表型在进展速度、分布、终末期聚集体水平和组织病理学方面存在差异。总之，我们的数据表明，聚集菌株是朊病毒，它们传播 hSOD1 的模板化、扩散聚集，导致致命的 ALS 样疾病。

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