Neurometabolism Research Lab., Hospital Nacional de Paraplejicos, SESCAM, Toledo, Spain.
Centro de Investigación en Salud (CEINSA), Universidad de Almería, Almería, Spain.
Brain Behav. 2022 Jan;12(1):e2465. doi: 10.1002/brb3.2465. Epub 2021 Dec 21.
Targeting leptin could represent a rational strategy to treat amyotrophic lateral sclerosis (ALS), as previously clinical studies have shown its levels to be associated with a lower risk of ALS disease. However, very little is known about the potential influence of leptin in altering disease progression in ALS, as it has thus far been correlated with the protection exerted by increased fat mass stores.
We studied the impact of leptin treatment beginning at 42-days of age (asymptomatic stage of disease) in the TDP-43 (TDP43 ) transgenic (Tg) ALS mouse model.
Our study shows that leptin treatment was associated with altered expression of adipokines and metabolic proteins in TDP43 mice. We also observed that weight loss decline was less prominent after leptin treatment in TDP43 mice relative to vehicle-treated animals. In TDP43 mice treated with leptin the disease duration lasted longer along with an improvement in motor performance relative to vehicle-treated animals.
Collectively, our results support leptin as a potential novel treatment approach for ALS.
靶向瘦素可能代表了一种治疗肌萎缩侧索硬化症（ALS）的合理策略，因为之前的临床研究表明，其水平与 ALS 疾病的风险降低相关。然而，关于瘦素在改变 ALS 疾病进展方面的潜在影响知之甚少，因为迄今为止，它与增加脂肪质量储存所发挥的保护作用相关。
我们研究了从 42 天龄（疾病无症状阶段）开始用瘦素治疗 TDP-43（TDP43）转基因（Tg）ALS 小鼠模型的影响。
我们的研究表明，瘦素治疗与 TDP43 小鼠脂肪因子和代谢蛋白的表达改变有关。我们还观察到，与接受载体治疗的动物相比，接受瘦素治疗的 TDP43 小鼠体重下降不那么明显。与接受载体治疗的动物相比，接受瘦素治疗的 TDP43 小鼠的疾病持续时间更长，运动性能得到改善。
总的来说，我们的结果支持瘦素作为 ALS 的一种潜在新型治疗方法。
