Cerebral deposition of abnormally aggregated α-synuclein (αSyn) is a neuropathological hallmark of Parkinson’s disease (PD). PD-associated αSyn (αSyn^PD) aggregates can act as proteinaceous nuclei (“seeds”) able of self-templated propagation. Since this is strikingly reminiscent to properties of proteinaceous infectious particles (prions), lessons learned from prion diseases suggest to test whether transferred αSyn^PD can propagate and induce neurological impairments or disease in a new host. Two studies that addressed this question provided divergent results. Intracerebral (i.c.) injection of Lewy body extracts from PD patients caused cerebral αSyn pathology, as well as nigrostriatal neurodegeneration, of wild-type mice and macaques, with the mice also showing motor impairments (Recasens et al. 2014, Ann Neurol 75:351–362). In contrast, i.c. transmission of homogenates from PD brains did not stimulate, after “> 360” days post-injection (dpi), pathological αSyn conversion or clinical symptoms in transgenic TgM83^+/− mice hemizygously expressing mutated (A53T) human αSyn (Prusiner et al. 2015, PNAS 112:E5308–E5317). To advance the assessment of possible αSyn^PD hazards by providing further data, we examined neuropathological and clinical effects upon i.c. transmission of brain, stomach wall and muscle tissue as well as blood from PD patients in TgM83^+/− mice up to 612 dpi. This revealed a subtle, yet distinctive stimulation of localized αSyn aggregation in the somatodendritic compartment and dystrophic neurites of individual or focally clustered cerebral neurons after challenge with brain and stomach wall homogenates. No such effect was observed with transmitted blood or homogenized muscle tissue. The detected stimulation of αSyn aggregation was not accompanied by apparent motor impairments or overt neurological disease in TgM83^+/− mice. Our study substantiated that transmitted αSyn^PD seeds, including those from the stomach wall, are able to propagate in new mammalian hosts. The consequences of such propagation and potential safeguards need to be further investigated.

异常聚集的 α-突触核蛋白 (αSyn) 的脑沉积是帕金森病 (PD) 的神经病理学标志。PD 相关的 αSyn (αSyn ^PD ) 聚集体可以作为能够自我模板化繁殖的蛋白质核（“种子”）。由于这与蛋白质传染性颗粒（朊病毒）的特性非常相似，因此从朊病毒疾病中汲取的教训建议测试是否转移了 αSyn ^PD可以在新宿主中传播和诱导神经损伤或疾病。解决这个问题的两项研究提供了不同的结果。脑内 (ic) 注射 PD 患者的路易体提取物导致野生型小鼠和猕猴的脑 αSyn 病理学以及黑质纹状体神经变性，这些小鼠也表现出运动障碍 (Recasens 等人 2014, Ann Neurol 75:351 –362)。相反，在注射后（dpi）“> 360”天后，来自 PD 大脑的匀浆的 ic 传输不会刺激半合子表达突变（A53T）人αSyn（Prusiner）的转基因 TgM83 ^+/-小鼠的病理性 αSyn 转化或临床症状等人，2015，PNAS 112：E5308–E5317）。推进对可能的 αSyn ^PD的评估通过提供进一步的数据，我们在高达 612 dpi的 TgM83 ^+/-小鼠中检查了 ic 传输对脑、胃壁和肌肉组织以及 PD 患者血液的神经病理学和临床影响。这揭示了在用脑和胃壁匀浆攻击后，对体树突区的局部 αSyn 聚集和单个或局部聚集的脑神经元的营养不良神经突的微妙而独特的刺激。传输的血液或均质化的肌肉组织没有观察到这种影响。^{在 TgM83 +/-}小鼠中检测到的 αSyn 聚集刺激不伴有明显的运动障碍或明显的神经疾病。我们的研究证实了传播的αSyn ^PD种子，包括来自胃壁的种子，能够在新的哺乳动物宿主中繁殖。这种传播和潜在保障措施的后果需要进一步调查。