Samson F E, Nelson S R
Department of Molecular and Integrative Physiology, Ralph L Smith Research Center, University of Kansas Medical Center, Kansas City 66160-7336, USA.
Cell Mol Biol (Noisy-le-grand). 2000 Jun;46(4):699-707.
In this overview we bring together certa in facts and concepts that support the theory that the aging of "disease-free" brain is a consequence of the accumulated cellular-molecular modifications caused by oxygen free radicals. The relevance of transition metals, especially iron ions, in the production of oxygen free radicals, initiation of oxidative chain-reactions and in site-specific molecular modifications is documented. Mitochondria are identified as the major source of oxygen free radicals, and mitochondrial DNA is a likely target. Special attention is given to iron-sulfur clusters as sources of reactive iron and sites of modifications. Potential mechanisms by which oxygen free radicals can alter membrane receptors and intracellular signaling are cited. Although the evidence is still correlative, the oxygen free radical theory has strong experimental support and has promise for facilitating a better understanding of the "disease-free", aging brain.
在本综述中，我们汇总了某些事实和概念，这些事实和概念支持了这样一种理论，即“无疾病”大脑的老化是由氧自由基引起的细胞分子修饰积累的结果。过渡金属，尤其是铁离子，在氧自由基的产生、氧化链反应的引发以及位点特异性分子修饰中的作用已得到证实。线粒体被确定为氧自由基的主要来源，线粒体DNA可能是靶点。特别关注铁硫簇作为活性铁的来源和修饰位点。文中引用了氧自由基改变膜受体和细胞内信号传导的潜在机制。尽管证据仍然是相关性的，但氧自由基理论有强有力的实验支持，有望促进对“无疾病”的老化大脑的更好理解。
