在肌性侧面硬化症中,超氧化物脱酶异体化算法的吉布斯能量可变生存率
Yunhua Shi1, Mark J Acerson1, Alireza Abdolvahabi1
1Department of Chemistry and Biochemistry, Baylor University , Waco, Texas 76798-7348, United States.
Journal of the American Chemical Society
|April 8, 2016
概括
突变的铜超氧化酶 (SOD1) 的亚单元交换与ALS的进展有关. 有利的异构化热力学与较短的患者存活率相关,这表明SOD1相关的肌性侧面硬化症的治疗标.
科学领域:
- 生物化学
- 神经科学
- 遗传学
背景情况:
- 肌缩侧面硬化 (ALS) 是一种神经退行性疾病.
- 突变的铜超氧化酶 (SOD1) 参与了ALS的发病.
- 野生类型和突变SOD1之间的子单位交换是一个可疑的关键事件.
研究的目的:
- 量化7种临床多样化的ALS变异型Apo-SOD1蛋白的异构化速率和热力学.
- 调查异体化参数与患者生存时间之间的相关性.
- 评估化对子单位交换动态的影响.
主要方法:
- 用毛细管区电泳来测量异体化率和吉布斯自由能量 (ΔGHet).
- 分析了七种临床上不同的ALS变体的apo- SOD1蛋白质.
- 对 ΔGHet,异体化率和患者生存数据进行了相关性分析.
主要成果:
- 在 ΔGHet 和患者存活时间之间发现了强烈的相关性 (R(2) = 0. 98).
- 更有利的 ΔGHet 与更短的存活时间 (4. 8 年/ kJ) 相关.
- 异体化率与生存率或发病年龄没有相关性.
- 化显著降低了小单位汇率,但影响 ΔGHet 的程度很小.
结论:
- 异体化热力学是SOD1相关的ALS生存的一个重要预测因素.
- 针对异构体热力学为SOD1-ALS提供了潜在的治疗策略.
- 了解亚单位交换机制对于开发有效的ALS治疗至关重要.
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