Abstract：
Synucleinopathies are neurodegenerative diseases characterized by the accumulation of α-synuclein protein aggregates in the neurons and glial cells. Both ex vivo and in vitro α-synuclein fibrils tend to show polymorphism. Polymorphism results in structure variations among fibrils originating from a single polypeptide/protein. The polymorphs usually have different biophysical, biochemical and pathogenic properties. The various pathologies of a single disease might be associated with distinct polymorphs. Similarly, in the case of different synucleinopathies, each condition might be associated with a different polymorph. Fibril formation is a nucleation-dependent process involving the formation of transient and heterogeneous intermediates from monomers. Polymorphs are believed to arise from heterogeneous oligomer populations because of distinct selection mechanisms in different conditions. To test this hypothesis, we isolated and incubated different intermediates during in vitro fibrillization of α-synuclein to form different polymorphs. Here, we report 13C and 15N chemical shifts and the secondary structure of fibrils prepared from the helical intermediate using solid-state nuclear magnetic spectroscopy.
摘要：
突触核蛋白病是神经退行性疾病,其特征在于α-突触核蛋白聚集体在神经元和神经胶质细胞中的积累。离体和体外α-突触核蛋白原纤维都倾向于显示多态性。多态性导致源自单一多肽/蛋白质的原纤维之间的结构变化。多晶型物通常具有不同的生物物理，生化和致病特性。单一疾病的各种病理可能与不同的多态性有关。同样，在不同的突触核蛋白病的情况下，每个条件可能与不同的多晶型有关。原纤维的形成是一个依赖成核的过程，涉及从单体中形成瞬时和非均相中间体。由于在不同条件下的不同选择机制,多晶型物被认为是由异质寡聚体群体产生的。为了检验这个假设，我们在α-突触核蛋白的体外纤维化过程中分离并孵育了不同的中间体以形成不同的多晶型物。这里,我们报告了13C和15N化学位移以及使用固态核磁光谱法从螺旋中间体制备的原纤维的二级结构。
