加拿大多伦多大学Joel C. Watts组的最新研究发现，α-突触核蛋白菌可以针对不同的大脑区域和细胞类型。相关论文在线发表在2019年12月2日的《自然—神经科学》上。

研究人员发现，用不同的重组菌或脑源性α-突触核蛋白聚集体，感染转基因小鼠会产生临床和病理上不同的疾病。在神经系统疾病的特征、发病时间、脑α-突触核蛋白沉积物的形态，以及诱导形成聚集体的构象特征方面观察到菌株特异性差异。而且，不同的菌株靶向大脑内不同的细胞群和细胞类型，这与在人类突触核病中观察到的选择性靶向相似。连续传代后，这些菌株很好地保持了菌株特异性的临床、病理和生化差异，这意味着α-突触核蛋白通过朊病毒样构象模板传播。因此，致病性α-突触核蛋白具有朊病毒的标志性特征，这些证据表明突触核蛋白病之间的疾病异质性是由不同的α-突触核蛋白菌株引起的。

据了解，诸如帕金森病和多系统萎缩症之类的突触核蛋白疾病，临床和病理学差异可能是由独特的α-突触核蛋白菌的聚集造成的，类似于朊病毒疾病中发生的情况。

附：英文原文

Title: α-Synuclein strains target distinct brain regions and cell types

Author: Angus Lau, Raphaella W. L. So, Heather H. C. Lau, Jason C. Sang, Alejandro Ruiz-Riquelme, Shelaine C. Fleck, Erica Stuart, Sindhu Menon, Naomi P. Visanji, Georg Meisl, Rania Faidi, Maria M. Marano, Cian Schmitt-Ulms, Zhilan Wang, Paul E. Fraser, Anurag Tandon, Bradley T. Hyman, Holger Wille, Martin Ingelsson, David Klenerman, Joel C. Watts

Issue&Volume: 2019-12-02

Abstract: The clinical and pathological differences between synucleinopathies such as Parkinson’s disease and multiple system atrophy have been postulated to stem from unique strains of α-synuclein aggregates, akin to what occurs in prion diseases. Here we demonstrate that inoculation of transgenic mice with different strains of recombinant or brain-derived α-synuclein aggregates produces clinically and pathologically distinct diseases. Strain-specific differences were observed in the signs of neurological illness, time to disease onset, morphology of cerebral α-synuclein deposits and the conformational properties of the induced aggregates. Moreover, different strains targeted distinct cellular populations and cell types within the brain, recapitulating the selective targeting observed among human synucleinopathies. Strain-specific clinical, pathological and biochemical differences were faithfully maintained after serial passaging, which implies that α-synuclein propagates via prion-like conformational templating. Thus, pathogenic α-synuclein exhibits key hallmarks of prion strains, which provides evidence that disease heterogeneity among the synucleinopathies is caused by distinct α-synuclein strains.

DOI: 10.1038/s41593-019-0541-x

Source: https://www.nature.com/articles/s41593-019-0541-x