Department of Public Health/Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Biochem Biophys Res Commun. 2011 Aug 19;412(1):32-8. doi: 10.1016/j.bbrc.2011.07.027. Epub 2011 Jul 21.
Deposition of fibrillar α-synuclein as Lewy bodies is the neuropathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Apart from α-synuclein, these intraneuronal inclusions contain over 250 different proteins. The actin binding protein gelsolin, has previously been suggested to be part of the Lewy body, but its potential role in α-synuclein aggregation remains unknown. Here, we studied the association between gelsolin and α-synuclein in brain tissue from PD and DLB patients as well as in a cell model for α-synuclein aggregation. Moreover, the potential effect of gelsolin on α-synuclein fibrillization was also investigated. Our data demonstrate that gelsolin co-occured with α-synuclein in Lewy bodies from affected human brain as well as with Lewy body-like inclusions in α-synuclein over expressing cells. Furthermore, in the presence of calcium chloride, gelsolin was found to enhance the aggregation rate of α-synuclein in vitro. Moreover, no apparent structural differences could be observed between fibrils formed in the presence or absence of gelsolin. Further studies on gelsolin and other Lewy body associated proteins are warranted to learn more about their potential role in the α-synuclein aggregation process.
纤维状α-突触核蛋白的沉积是帕金森病 (PD) 和路易体痴呆 (DLB) 的神经病理学标志。除了α-突触核蛋白，这些神经元内包涵体还含有 250 多种不同的蛋白质。肌动蛋白结合蛋白凝胶蛋白先前被认为是路易小体的一部分，但它在α-突触核蛋白聚集中的潜在作用仍不清楚。在这里，我们研究了在 PD 和 DLB 患者的脑组织以及用于α-突触核蛋白聚集的细胞模型中，凝胶蛋白与α-突触核蛋白之间的关联。此外，还研究了凝胶蛋白对α-突触核蛋白纤维化的潜在影响。我们的数据表明，凝胶蛋白与受影响人脑中的路易小体中的α-突触核蛋白以及α-突触核蛋白过表达细胞中的路易体样包涵体共同存在。此外，在氯化钙存在的情况下，发现凝胶蛋白可增强α-突触核蛋白在体外的聚集速率。此外，在有或没有凝胶蛋白存在的情况下形成的纤维之间没有观察到明显的结构差异。需要进一步研究凝胶蛋白和其他路易体相关蛋白，以了解它们在α-突触核蛋白聚集过程中的潜在作用。
