Romero-Sanz Silvia, Caldero-Escudero Elena, Álvarez-Illera Pilar, Santo-Domingo Jaime, de la Fuente Sergio, García-Casas Paloma, Fonteriz Rosalba I, Montero Mayte, Álvarez Javier
Departamento de Bioquímica y Biología Molecular y Fisiología, Facultad de Medicina, Universidad de Valladolid, 47005 Valladolid, Spain.
Unidad de Excelencia Instituto de Biomedicina y Genética Molecular (IBGM), Universidad de Valladolid y Consejo Superior de Investigaciones Científicas (CSIC), 47005 Valladolid, Spain.
Int J Mol Sci. 2025 Apr 4;26(7):3371. doi: 10.3390/ijms26073371.
We have previously shown that the compound CGP37157, a mitochondrial Na/Ca exchanger inhibitor, increases lifespan and improves muscle and mitochondrial structure during aging in wild-type nematodes. We used here a rotenone model of Parkinson's disease in to test the ability of CGP37157 to rescue the alterations induced by the toxicant. Rotenone, a mitochondrial respiratory chain complex I inhibitor, reduced worm lifespan and muscle activity, measured as worm mobility, pharyngeal pumping, and defecation rate. It also increased ROS production, decreased mitochondrial membrane potential, and disorganized mitochondrial structure. Moreover, it induced degeneration of dopaminergic neurons and changes in behavior. We found that CGP37157 produced a partial or complete reversal of most of these alterations. These results are consistent with our previous proposal that Ca homeostasis is important in the development of neurodegenerative diseases, and modulation of the Ca signaling toolkit may be a novel target for their treatment.
我们之前已经表明，化合物CGP37157，一种线粒体钠/钙交换抑制剂，可延长野生型线虫衰老过程中的寿命，并改善肌肉和线粒体结构。我们在此使用帕金森病的鱼藤酮模型来测试CGP37157挽救由该毒物引起的改变的能力。鱼藤酮是一种线粒体呼吸链复合体I抑制剂，可缩短线虫寿命并降低肌肉活性，通过线虫运动能力、咽泵动和排便率来衡量。它还会增加活性氧的产生，降低线粒体膜电位，并破坏线粒体结构。此外，它会导致多巴胺能神经元变性和行为改变。我们发现CGP37157使这些改变中的大多数得到了部分或完全逆转。这些结果与我们之前的观点一致，即钙稳态在神经退行性疾病的发展中很重要，并且调节钙信号工具包可能是其治疗的一个新靶点。
