Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China.
Biomolecules. 2021 Aug 29;11(9):1287. doi: 10.3390/biom11091287.
As a pathological biomarker of Parkinson's disease, α-synuclein is thought to be a prion-like protein, but evidence for the transmission of α-synuclein from blood to the brain is unclear. The goals of this study were to determine whether blood-derived α-synuclein could enter the brains of mice and whether α-synuclein in the brain could be cleared by parabiosis. Heterochronic parabiosis was performed on transgenic mice (A53T mice) and wildtype mice. The levels of human α-synuclein in the blood and substantia nigra of wildtype mice were significantly increased after 4-month parabiosis with A53T mice. Moreover, the expression of α-synuclein filament, but not of total α-synuclein, was significantly increased in the substantia nigra of wildtype mice that were paired with A53T mice. However, the levels of human α-synuclein displayed no significant change in the serum, blood, or substantia nigra of A53T mice. These results provide direct evidence that pathological α-synuclein can be transmitted from blood to the brain in the heterochronic parabiosis system; however, it appears to be difficult to clear it from the brain in a short period of time.
作为帕金森病的病理生物标志物，α-突触核蛋白被认为是一种类朊病毒蛋白，但血液中的α-突触核蛋白向大脑传播的证据尚不清楚。本研究的目的是确定血液来源的α-突触核蛋白是否可以进入小鼠的大脑，以及脑内的α-突触核蛋白是否可以通过异时性联体动物清除。对转基因小鼠（A53T 小鼠）和野生型小鼠进行了异时性联体动物实验。与 A53T 小鼠进行 4 个月的联体动物实验后，野生型小鼠血液和黑质中的人α-突触核蛋白水平显著升高。此外，与 A53T 小鼠配对的野生型小鼠黑质中α-突触核蛋白丝的表达显著增加，但总α-突触核蛋白的表达没有显著增加。然而，A53T 小鼠的血清、血液或黑质中人α-突触核蛋白的水平没有显示出显著变化。这些结果提供了直接证据，表明在异时性联体动物系统中，病理性α-突触核蛋白可以从血液传播到大脑；然而，在短时间内似乎难以从大脑中清除它。
