Department of Neuroscience, Developmental and Regenerative Biology, The University of Texas at San Antonio (UTSA), San Antonio, TX 78249, USA.
Int J Mol Sci. 2023 Aug 6;24(15):12486. doi: 10.3390/ijms241512486.
The progressive deterioration of function and structure of brain cells in neurodegenerative diseases is accompanied by mitochondrial dysfunction, affecting cellular metabolism, intracellular signaling, cell differentiation, morphogenesis, and the activation of programmed cell death. However, most of the efforts to develop therapies for Alzheimer's and Parkinson's disease have focused on restoring or maintaining the neurotransmitters in affected neurons, removing abnormal protein aggregates through immunotherapies, or simply treating symptomatology. However, none of these approaches to treating neurodegeneration can stop or reverse the disease other than by helping to maintain mental function and manage behavioral symptoms. Here, we discuss alternative molecular targets for neurodegeneration treatments that focus on mitochondrial functions, including regulation of calcium ion (Ca) transport, protein modification, regulation of glucose metabolism, antioxidants, metal chelators, vitamin supplementation, and mitochondrial transference to compromised neurons. After pre-clinical evaluation and studies in animal models, some of these therapeutic compounds have advanced to clinical trials and are expected to have positive outcomes in subjects with neurodegeneration. These mitochondria-targeted therapeutic agents are an alternative to established or conventional molecular targets that have shown limited effectiveness in treating neurodegenerative diseases.
在神经退行性疾病中，脑细胞的功能和结构逐渐恶化伴随着线粒体功能障碍，影响细胞代谢、细胞内信号转导、细胞分化、形态发生和程序性细胞死亡的激活。然而，大多数开发阿尔茨海默病和帕金森病疗法的努力都集中在恢复或维持受影响神经元中的神经递质、通过免疫疗法清除异常蛋白聚集体，或仅仅治疗症状上。然而，除了帮助维持精神功能和管理行为症状外，这些治疗神经退行性变的方法都无法阻止或逆转疾病。在这里，我们讨论了针对神经退行性变治疗的替代分子靶点，这些靶点集中在线粒体功能上，包括钙离子（Ca）转运的调节、蛋白质修饰、葡萄糖代谢的调节、抗氧化剂、金属螯合剂、维生素补充剂和线粒体转移到受损神经元。在临床前评估和动物模型研究之后，其中一些治疗化合物已进入临床试验，预计在神经退行性变患者中会有积极的结果。这些靶向线粒体的治疗剂是一种替代已建立或传统的分子靶点的方法，这些靶点在治疗神经退行性疾病方面显示出有限的效果。
