Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport.
Neuron-to-neuron transmission of α-synuclein fibrils through axonal transport.
复制标题
DOI：
10.1002/ana.23747
复制
发表时间：
2012-10
影响因子：
11.2
通讯作者：
Brahic, Michel
中科院分区：
文献类型：
--
作者：
Freundt, Eric C.;Maynard, Nate;Clancy, Eileen K.;Roy, Shyamali;Bousset, Luc;Sourigues, Yannick;Covert, Markus;Melki, Ronald;Kirkegaard, Karla;Brahic, Michel
The lesions of Parkinson's disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded α-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous α-synuclein to misfold. Here, we characterized and quantified the axonal transport of α-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport. We grew primary cortical mouse neurons in microfluidic devices to separate soma from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent α-synuclein fibrils and their transfer to second-order neurons. Fibrillar α-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar α-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts. These results support the hypothesis that the progression of Parkinson's disease can be caused by neuron-to-neuron spread of α-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be transsynaptic gives hope that α-synuclein fibrils could be intercepted by drugs during the extra-cellular phase of their journey.
登录
查看更多内容
影响因子：
82.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
4.8
作者：
Danzer, Karin M.;Ruf, Wolfgang P.;McLean, Pamela J.
通讯作者：
McLean, Pamela J.
影响因子：
4.2
作者：
Mougenot, Anne-Laure;Nicot, Simon;Baron, Thierry
通讯作者：
Baron, Thierry
DOI：
10.1084/jem.20112457
发表时间：
2012-05-07
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luk KC;Kehm VM;Zhang B;O'Brien P;Trojanowski JQ;Lee VM
通讯作者：
Lee VM
影响因子：
5.3
作者：
Roy, Subhojit;Winton, Matthew J.;Lee, Virginia M. -Y.
通讯作者：
Lee, Virginia M. -Y.