Butterfield D A, Martin L, Carney J M, Hensley K
Department of Chemistry, University of Kentucky, Lexington 40506, USA.
Life Sci. 1996;58(3):217-28. doi: 10.1016/0024-3205(95)02279-1.
Amyloid beta peptides (A beta s) are found in abnormally high accumulations in brains of persons with Alzheimer's disease, and are believed to contribute to cognitive decline in this disorder. Synthetic A beta and its peptide fragment 25-35 [A beta (25-35)] are toxic to cells in culture; however, the exact mechanism of amyloid peptide toxicity is not known. An emerging hypothesis contends that A beta toxicity results from peptide-mediated free radical reactions and generation of reactive oxygen species. Recently, we reported that reactivity of A beta toward the oxidation-sensitive enzyme glutamine synthetase is related to the peptide's reactivity toward the spin trap phenyl-tert-butyl nitrone (PBN). Neuronal damage may be due, in part, to oxidative processes initiated by amyloid-derived free radicals species. This work presents evidence from electron paramagnetic resonance (EPR) spin labeling techniques and spectrophotometric assays that a portion of synthetic A beta (25-35) demonstrates hydrogen peroxide-like reactivity toward Fe2+, nitroxide spin probes, and neocortical synaptasomal membrane proteins. These results are discussed with reference to free radical membrane damage and neurotoxicity in Alzheimer's disease.
淀粉样β肽（Aβ）在阿尔茨海默病患者的大脑中异常大量积聚，据信这会导致该疾病的认知功能衰退。合成的Aβ及其肽片段25 - 35 [Aβ(25 - 35)] 对培养中的细胞有毒性；然而，淀粉样肽毒性的确切机制尚不清楚。一种新出现的假说认为，Aβ毒性源于肽介导的自由基反应和活性氧的产生。最近，我们报道了Aβ对氧化敏感酶谷氨酰胺合成酶的反应性与该肽对自旋捕获剂苯基叔丁基硝酮（PBN）的反应性有关。神经元损伤可能部分归因于淀粉样衍生自由基引发的氧化过程。这项工作通过电子顺磁共振（EPR）自旋标记技术和分光光度法检测提供了证据，表明一部分合成的Aβ(25 - 35) 对Fe2 +、氮氧化物自旋探针和新皮质突触体膜蛋白表现出类似过氧化氢的反应性。本文结合自由基膜损伤和阿尔茨海默病中的神经毒性对这些结果进行了讨论。
