Neuronal Survival Unit, BMC B11, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, Sölvegatan 19, 221 84, Lund, Sweden,
Acta Neuropathol. 2013 Oct;126(4):555-73. doi: 10.1007/s00401-013-1160-3. Epub 2013 Aug 8.
α-Synuclein (α-syn) is a protein prevalent in neural tissue and known to undergo axonal transport. Intracellular α-syn aggregates are a hallmark of Parkinson's disease (PD). Braak and collaborators have suggested that in people who are destined to eventually develop PD, α-syn aggregate pathology progresses following a stereotypic pattern, starting in the olfactory bulb (OB) and the gut. α-Synuclein aggregates are postulated to spread to interconnected brain regions over several years. Thus, propagation of the pathology via neural pathways can potentially explain how α-syn aggregates spread in PD. We have now studied if α-syn can transfer from the OB to other brain structures through neural connections, by injecting different molecular species of human α-syn (monomers, oligomers, fibrils) into the OB of wild-type mice. We found that non-fibrillar human α-syn is taken up very quickly by OB neurons. Within minutes to hours, it is also found in neurons in structures connected to the OB. Conversely, when we injected bovine serum albumin used as a control protein, we found that it does not diffuse beyond the OB, is rarely taken up by OB cells, and does not transfer to other structures. Taken together, our results show that OB cells readily take up α-syn, and that monomeric and oligomeric, but not fibrillar, forms of α-syn are rapidly transferred to interconnected structures within the timeframe we explored. Our results support the idea that α-syn can transfer along neural pathways and thereby contribute to the progression of the α-syn-related pathology.
α-突触核蛋白（α-syn）是一种在神经组织中普遍存在的蛋白质，已知其可进行轴突运输。细胞内的 α-突触核蛋白聚集体是帕金森病（PD）的一个标志。Braak 及其合作者提出，在那些注定最终会患上 PD 的人中，α-syn 聚集体病理学按照一种刻板的模式进展，从嗅球（OB）和肠道开始。α-突触核蛋白聚集体被假设在几年内扩散到相互连接的大脑区域。因此，通过神经途径传播病理学可以解释 PD 中 α-syn 聚集体的扩散方式。我们现在通过将不同种类的人源 α-syn（单体、寡聚体、纤维）注射到野生型小鼠的 OB 中，研究了 α-syn 是否可以通过神经连接从 OB 转移到其他大脑结构。我们发现非纤维状的人源 α-syn 很快被 OB 神经元摄取。在几分钟到几小时内，它也在与 OB 相连的结构中的神经元中被发现。相反，当我们注射作为对照蛋白的牛血清白蛋白时，我们发现它不会扩散到 OB 之外，很少被 OB 细胞摄取，也不会转移到其他结构。总之，我们的结果表明，OB 细胞很容易摄取 α-syn，并且单体和寡聚体形式的 α-syn 而不是纤维状形式的 α-syn 可以在我们研究的时间范围内迅速转移到相互连接的结构中。我们的结果支持这样一种观点，即 α-syn 可以沿着神经途径转移，从而有助于与 α-syn 相关的病理学的进展。
