Phosphorylation of endogenous α-synuclein induced by extracellular seeds initiates at the pre-synaptic region and spreads to the cell body.
Phosphorylation of endogenous α-synuclein induced by extracellular seeds initiates at the pre-synaptic region and spreads to the cell body.
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DOI：
10.1038/s41598-022-04780-4
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发表时间：
2022-01-21
影响因子：
4.6
通讯作者：
Hasegawa M
中科院分区：
文献类型：
--
作者：
Awa S;Suzuki G;Masuda-Suzukake M;Nonaka T;Saito M;Hasegawa M
磷酸化α-突触核蛋白聚集体的积累与几种疾病有关，例如帕金森病（PD）和路易体痴呆（DLB），并被认为以朊病毒样方式传播。阐明α-突触核蛋白的朊病毒样传递机制对于开发这些疾病的治疗方法非常重要，但对其细节知之甚少。在这里，我们将α-突触核蛋白纤维注射到野生型小鼠的脑中，并检查了磷酸化α-突触核蛋白积累诱导的早期阶段。我们发现脑内注射后几天内就出现了磷酸化的α-synuclein。最初在突触前区观察到，随后将其定位扩展到轴突和细胞体。这些结果表明，细胞外α-突触核蛋白纤维被摄取到突触前区域，并依赖于种子将那里丰富的内源性正常α-突触核蛋白转化为异常磷酸化形式，然后通过轴突转运到细胞体。
Accumulation of phosphorylated α-synuclein aggregates has been implicated in several diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and is thought to spread in a prion-like manner. Elucidating the mechanisms of prion-like transmission of α-synuclein is important for the development of therapies for these diseases, but little is known about the details. Here, we injected α-synuclein fibrils into the brains of wild-type mice and examined the early phase of the induction of phosphorylated α-synuclein accumulation. We found that phosphorylated α-synuclein appeared within a few days after the intracerebral injection. It was observed initially in presynaptic regions and subsequently extended its localization to axons and cell bodies. These results suggest that extracellular α-synuclein fibrils are taken up into the presynaptic region and seed-dependently convert the endogenous normal α-synuclein that is abundant there to an abnormal phosphorylated form, which is then transported through the axon to the cell body.
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DOI：
10.1126/science.aah3374
发表时间：
2016-09-30
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mao X;Ou MT;Karuppagounder SS;Kam TI;Yin X;Xiong Y;Ge P;Umanah GE;Brahmachari S;Shin JH;Kang HC;Zhang J;Xu J;Chen R;Park H;Andrabi SA;Kang SU;Gonçalves RA;Liang Y;Zhang S;Qi C;Lam S;Keiler JA;Tyson J;Kim D;Panicker N;Yun SP;Workman CJ;Vignali DA;Dawson VL;Ko HS;Dawson TM
通讯作者：
Dawson TM
影响因子：
4.6
作者：
Hoffmann, Anna-Carin;Minakaki, Georgia;Xiang, Wei
通讯作者：
Xiang, Wei
影响因子：
14.5
作者：
Colom-Cadena, Marti;Pegueroles, Jordi;Lleo, Alberto
通讯作者：
Lleo, Alberto
影响因子：
16.6
作者：
Freixo F;Martinez Delgado P;Manso Y;Sánchez-Huertas C;Lacasa C;Soriano E;Roig J;Lüders J
通讯作者：
Lüders J
DOI：
10.1126/science.1227157
发表时间：
2012-11-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Luk KC;Kehm V;Carroll J;Zhang B;O'Brien P;Trojanowski JQ;Lee VM
通讯作者：
Lee VM