Kobayashi Masaki, Kim Jihoon, Kobayashi Natsuki, Han Sungwoong, Nakamura Chikashi, Ikebukuro Kazunori, Sode Koji
Department of Biotechnology, Graduate School of Engineering, Tokyo University of Agriculture and Technology, 184-8588 Tokyo, Koganei, Japan.
Biochem Biophys Res Commun. 2006 Oct 27;349(3):1139-44. doi: 10.1016/j.bbrc.2006.08.144. Epub 2006 Sep 1.
Pyrroloquinoline quinone (PQQ) is a noncovalently bound cofactor in the bacterial oxidative metabolism of alcohols. PQQ also exists in plants and animals. Due to its inherent chemical feature, namely its free-radical scavenging properties, PQQ has been drawing attention from both the nutritional and the pharmacological viewpoint. alpha-Synuclein, a causative factor of Parkinson's disease (PD), has the propensity to oligomerize and form fibrils, and this tendency may play a crucial role in its toxicity. We show that PQQ prevents the amyloid fibril formation and aggregation of alpha-synuclein in vitro in a PQQ-concentration-dependent manner. Moreover, PQQ forms a conjugate with alpha-synuclein, and this PQQ-conjugated alpha-synuclein is also able to prevent alpha-synuclein amyloid fibril formation. This is the first study to demonstrate the characteristics of PQQ as an anti-amyloid fibril-forming reagent. Agents that prevent the formation of amyloid fibrils might allow a novel therapeutic approach to PD. Therefore, together with further pharmacological approaches, PQQ is a candidate for future anti-PD reagent compounds.
吡咯喹啉醌（PQQ）是细菌酒精氧化代谢中一种非共价结合的辅因子。PQQ也存在于植物和动物中。由于其固有的化学特性，即自由基清除特性，PQQ从营养和药理学角度都受到了关注。α-突触核蛋白是帕金森病（PD）的致病因素之一，具有寡聚和形成纤维的倾向，这种倾向可能在其毒性中起关键作用。我们发现，PQQ在体外以浓度依赖的方式阻止α-突触核蛋白的淀粉样纤维形成和聚集。此外，PQQ与α-突触核蛋白形成共轭物，这种PQQ共轭的α-突触核蛋白也能够阻止α-突触核蛋白淀粉样纤维的形成。这是第一项证明PQQ作为抗淀粉样纤维形成试剂特性的研究。阻止淀粉样纤维形成的试剂可能为PD提供一种新的治疗方法。因此，与进一步的药理学方法一起，PQQ是未来抗PD试剂化合物的候选者。
