Moussa Charbel E-H, Wersinger Christophe, Rusnak Milan, Tomita York, Sidhu Anita
Department of Pediatrics, Georgetown University, Washington, DC 20007, USA.
Neurosci Lett. 2004 Nov 23;371(2-3):239-43. doi: 10.1016/j.neulet.2004.09.004.
Alpha-synuclein aggregates have been linked to the pathogenesis of Parkinson's disease (PD), with Lewy bodies (LBs) and Lewy neurites (LNs) constituting the pathological hallmarks in the brains of patients with PD and dementia with LBs. LBs are formed by the conversion of soluble monomers of alpha-synuclein into insoluble aggregates. Here we report an abnormal electrophoretic mobility, at a higher molecular weight (MW) than the expected theoretical MW, of both recombinant histidine-tagged human alpha-synuclein, human alpha-synuclein expressed in SH-SY5Y human neuroblastoma cells or Ltk(-) fibroblasts, and rat brain alpha-synuclein, on SDS-PAGE polyacrylamide, but not on Nu-PAGE gradient peptide, gels, suggesting possible alpha-synuclein data misinterpretations associated with gel electrophoresis. These studies raise important considerations about the type of protein gel electrophoresis system suitable to study the alterations of alpha-synuclein associated with neurodegeneration, PD and other synucleinopathies.
α-突触核蛋白聚集体与帕金森病（PD）的发病机制有关，路易小体（LBs）和路易神经突（LNs）是PD患者及路易小体痴呆患者大脑中的病理标志。LBs由α-突触核蛋白的可溶性单体转化为不溶性聚集体形成。在此，我们报告了在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）聚丙烯酰胺凝胶上，重组组氨酸标签化人α-突触核蛋白、在SH-SY5Y人神经母细胞瘤细胞或Ltk(-)成纤维细胞中表达的人α-突触核蛋白以及大鼠脑α-突触核蛋白的电泳迁移率异常，其分子量（MW）高于预期的理论MW，但在Nu-PAGE梯度肽凝胶上未出现这种情况，这表明与凝胶电泳相关的α-突触核蛋白数据可能存在误判。这些研究对适合研究与神经退行性变、PD及其他突触核蛋白病相关的α-突触核蛋白改变的蛋白质凝胶电泳系统类型提出了重要考虑。
