Laboratory of Inorganic Chemistry, Department of Chemical Engineering, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece.
J Inorg Biochem. 2012 Dec;117:342-50. doi: 10.1016/j.jinorgbio.2012.08.009. Epub 2012 Aug 24.
It is well known that iron dysregulation is involved in a number of processes involving genetic and non-genetic factors leading to neurodegeneration. Molecules bearing iron or influencing iron metabolism reflect directly into the levels of that redox active metal, present as Fe(II)/Fe(III), in the brain. In turn, iron level variations are associated with chemical reactivity disrupting iron homeostasis, generating variable neurotoxic iron forms and contributing to the vulnerability of cells toward oxidative stress and neuronal death in Alzheimer's disease (AD). Efforts to delineate the interactions of neurotoxic Fe(III) with low molecular mass substrates, relevant to cellular processes, led to the discovery of specific well-defined binary iron-quinate (FeQ) species. Poised to investigate the specific effects of a) well-defined forms of labile soluble Fe(III), b) the nature and chemistry of the ligand bound to Fe(III), and c) a natural metal ion binder - quinic acid - acting as a potential neuroprotectant toward iron toxicity, FeCl(3), FeQ, and free quinate were employed in in vitro studies involving primary rat hippocampal cultures. Three hour and 24-hour exposures of such cultures to Fe(III) reveal significant differential effects on both glial and neuronal cell survival linked to neurotoxicity of the specific yet variably composed complex forms of iron. The use of quinic acid both in the free and bound form to Fe(III) a) exemplifies essential structural and chemical attributes of naturally encountered metal ion binders promoting well-defined interactions with neurotoxic Fe(III), and b) signifies the potential linkage of labile Fe(III) chemical reactivity in neurodegeneration with natural substrate neuroprotection.
众所周知，铁代谢失调与多种涉及遗传和非遗传因素的过程有关，这些过程会导致神经退行性变。携带铁或影响铁代谢的分子直接反映了大脑中这种具有氧化还原活性的金属（Fe(II)/Fe(III)）的水平。反过来，铁水平的变化与化学活性有关，会破坏铁的动态平衡，产生不同的神经毒性铁形式，并导致细胞对阿尔茨海默病（AD）中的氧化应激和神经元死亡的易感性增加。为了阐明神经毒性 Fe(III)与与细胞过程相关的低分子量底物之间的相互作用，人们进行了努力，从而发现了特定的、定义明确的二元铁-奎宁酸（FeQ）物质。为了研究以下三个方面的具体影响：a）定义明确的可溶 Fe(III)形式；b）与 Fe(III)结合的配体的性质和化学性质；c）一种天然金属离子结合物-奎宁酸，作为铁毒性的潜在神经保护剂，FeCl(3)、FeQ 和游离奎宁酸被用于体外原代大鼠海马培养物的研究。这种培养物暴露于 Fe(III) 3 小时和 24 小时，显示出对神经毒性有显著的差异影响，与神经胶质细胞和神经元细胞的存活有关，这与特定但组成可变的铁复合物的神经毒性有关。游离和结合形式的奎宁酸对 Fe(III)的使用 a）例证了天然金属离子结合物所具有的重要结构和化学属性，促进了与神经毒性 Fe(III）的明确相互作用；b）表明了神经退行性变中不稳定 Fe(III)化学活性与天然底物神经保护之间的潜在联系。
