The Prion-Like Spreading of Alpha-Synuclein in Parkinson's Disease: Update on Models and Hypotheses.
The Prion-Like Spreading of Alpha-Synuclein in Parkinson's Disease: Update on Models and Hypotheses.
复制标题
帕金森病中α-突触核蛋白的朊病毒样扩散：模型和假设的更新。
DOI：
10.3390/ijms22158338
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发表时间：
2021-08-03
影响因子：
5.6
通讯作者：
Ferreira N
中科院分区：
文献类型：
--
作者：
Jan A;Gonçalves NP;Vaegter CB;Jensen PH;Ferreira N
突触前蛋白α-突触核蛋白（α-syn）的病理聚集和通过突触耦合神经解剖束的传播越来越被认为是帕金森病（PD）和相关突触核蛋白病的病理生理进展的基础。尽管尚未完全了解导致CNS中病理性α-syn蓄积扩散的精确分子机制，但越来越多的证据表明，重新α-syn错误折叠和/或聚集α-syn的神经元内化促进内源性α-syn单体的构象模板化，其机制令人联想到朊病毒。对介导错误折叠的α-syn的病理性神经元-神经元传播的生化和细胞因子的精细理解将可能阐明PD的病因并揭示治疗干预的新靶点。在这里，我们讨论了最近的发展，关于跨突触传播的α-syn病理学的神经元脆弱性的背景下的假设，并强调了潜在的效用，新的实验模型的突触核蛋白病。
The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies.
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DOI：
10.1073/pnas.0407146102
发表时间：
2005-02-01
影响因子：
11.1
作者：
Bertoncini, CW;Jung, YS;Zweckstetter, M
通讯作者：
Zweckstetter, M
影响因子：
4.8
作者：
Aasly JO;Johansen KK;Brønstad G;Warø BJ;Majbour NK;Varghese S;Alzahmi F;Paleologou KE;Amer DA;Al-Hayani A;El-Agnaf OM
通讯作者：
El-Agnaf OM
影响因子：
7.1
作者：
Barrenschee M;Zorenkov D;Böttner M;Lange C;Cossais F;Scharf AB;Deuschl G;Schneider SA;Ellrichmann M;Fritscher-Ravens A;Wedel T
通讯作者：
Wedel T
影响因子：
5.6
作者：
Adams JL;Lizarraga KJ;Waddell EM;Myers TL;Jensen-Roberts S;Modica JS;Schneider RB
通讯作者：
Schneider RB
影响因子：
5.4
作者：
Ayers, Jacob I.;Riffe, Cara J.;Giasson, Benoit I.
通讯作者：
Giasson, Benoit I.