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线粒体作为化疗靶点。

Mitochondria as targets for chemotherapy.

作者信息

Gogvadze Vladimir, Orrenius Sten, Zhivotovsky Boris

机构信息

Division of Toxicology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Apoptosis. 2009 Apr;14(4):624-40. doi: 10.1007/s10495-009-0323-0.

Abstract

Mitochondrial malfunctioning is implicated in the pathogenesis of a variety of disorders, including cancer and multiple neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. Disturbance of mitochondrial vital functions, e.g., production of ATP, calcium buffering capacity, and generation of reactive oxygen species, can be potentially involved in disease pathogenesis. Neurological disorders caused by mitochondrial deterioration are often associated with cell loss within specific brain regions. In contrast, mitochondrial alterations in tumor cells and the "Warburg effect" might lead to cell survival and resistance of tumor cells to chemotherapy. This review is devoted to the role of mitochondria in neurodegeneration and tumor formation, and describes how targeting of mitochondria can be beneficial in the therapy of these diseases, which affect a large human population.

摘要

线粒体功能障碍与多种疾病的发病机制有关,包括癌症和多种神经退行性疾病,如帕金森病、阿尔茨海默病、肌萎缩侧索硬化症和亨廷顿舞蹈症。线粒体重要功能的紊乱,如三磷酸腺苷(ATP)的产生、钙缓冲能力以及活性氧的生成,可能参与疾病的发病机制。由线粒体退化引起的神经疾病通常与特定脑区的细胞丢失有关。相比之下,肿瘤细胞中的线粒体改变和“瓦伯格效应”可能导致肿瘤细胞的存活及对化疗的抗性。本综述致力于探讨线粒体在神经退行性变和肿瘤形成中的作用,并描述靶向线粒体如何有益于这些影响大量人群的疾病的治疗。

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