Parkinson's disease from the gut.
Parkinson's disease from the gut.
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DOI：
10.1016/j.brainres.2018.01.010
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发表时间：
2018-08-15
期刊：
影响因子：
2.9
通讯作者：
Liddle RA
中科院分区：
文献类型：
--
作者：
Liddle RA
帕金森病（PD）是一种使人衰弱的神经退行性疾病，与震颤、强直、痴呆和胃肠道症状（如便秘、恶心和呕吐）相关。PD的病理学特征是脑和外周神经中的路易体。路易体的主要成分是神经元蛋白α-突触核蛋白。α-突触核蛋白的错误折叠赋予朊病毒样性质，使其能够在细胞间传播。错误折叠的α-突触核蛋白还充当模板，并诱导受体细胞中内源性α-突触核蛋白的错误折叠，导致形成寡聚体，所述寡聚体进展为原纤维并最终形成路易体。越来越多的证据表明，PD可能出现在肠道中。临床上，PD患者的胃肠道症状往往先于其他神经系统体征和肠神经中的α-突触核蛋白聚集体出现。重要的是，接受迷走神经切断术的患者发生PD的风险降低。在实验中，异常形式的α-突触核蛋白在它们出现在脑中之前出现在肠神经中，并且异常α-突触核蛋白注射到肠壁中扩散到迷走神经。摄入的毒素和肠道微生物群的改变可诱导α-突触核蛋白聚集和PD，然而，尚不清楚PD如何开始。最近，研究表明，被称为肠内分泌细胞（EECs）的肠道感觉细胞含有α-突触核蛋白，并与肠神经形成突触，从而提供了从肠道到大脑的连接。异常的α-突触核蛋白可能首先在EECs中发展并扩散到神经系统。α-突触核蛋白从肠道到神经系统的路径。肠内分泌细胞（EECs）表达α-突触核蛋白，并连接到含有α-突触核蛋白的肠神经。这种回路为肠道中的细菌或毒素提供了一种可能的途径，以诱导异常的α-突触核蛋白形成，这种异常的α-突触核蛋白可以转移到神经系统，从而引发帕金森病。
Parkinson’s disease (PD) is a debilitating neurodegenerative condition associated with tremor, rigidity, dementia, and gastrointestinal symptoms such as constipation, nausea and vomiting. The pathological hallmarks of PD are Lewy bodies in the brain and peripheral nerves. The major constituent of Lewy bodies is the neuronal protein α-synuclein. Misfolding of α-synuclein confers prion-like properties enabling its spread from cell to cell. Misfolded α-synuclein also serves as a template and induces misfolding of endogenous α-synuclein in recipient cells leading to the formation of oligomers that progress to fibrils and eventually Lewy bodies. Accumulating evidence suggests that PD may arise in the gut. Clinically, gastrointestinal symptoms often appear in patients before other neurological signs and aggregates of α-synuclein have been found in enteric nerves of PD patients. Importantly, patients undergoing vagotomy have a reduced risk of developing PD. Experimentally, abnormal forms of α-synuclein appear in enteric nerves before they appear in the brain and injection of abnormal α-synuclein into the wall of the intestine spreads to the vagus nerve. Ingested toxins and alterations in gut microbiota can induce α-synuclein aggregation and PD, however, it is not known how PD starts. Recently, it has been shown that sensory cells of the gut known as enteroendocrine cells (EECs) contain α-synuclein and synapse with enteric nerves, thus providing a connection from the gut to the brain. It is possible that abnormal α-synuclein first develops in EECs and spreads to the nervous system. A path for α-synuclein from the gut to the nervous system. Enteroendocrine cells (EECs) express α-synuclein and connect to α-synuclein-containing enteric nerves. This circuit provides a possible route for bacteria or toxins in the gut to induce abnormal α-synuclein formation that could transfer to the nervous system to initiate Parkinson’s disease.
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影响因子：
15.1
作者：
Danzer KM;Kranich LR;Ruf WP;Cagsal-Getkin O;Winslow AR;Zhu L;Vanderburg CR;McLean PJ
通讯作者：
McLean PJ
影响因子：
3.7
作者：
Angot E;Steiner JA;Lema Tomé CM;Ekström P;Mattsson B;Björklund A;Brundin P
通讯作者：
Brundin P
DOI：
10.1093/jnen/61.5.413
发表时间：
2002-05-01
影响因子：
3.2
作者：
Del Tredici, K;Rüb, U;Braak, H
通讯作者：
Braak, H
影响因子：
10.4
作者：
Chen H;Burton EA;Ross GW;Huang X;Savica R;Abbott RD;Ascherio A;Caviness JN;Gao X;Gray KA;Hong JS;Kamel F;Jennings D;Kirshner A;Lawler C;Liu R;Miller GW;Nussbaum R;Peddada SD;Rick AC;Ritz B;Siderowf AD;Tanner CM;Tröster AI;Zhang J
通讯作者：
Zhang J
影响因子：
15.9
作者：
Bohorquez, Diego V.;Shahid, Rafiq A.;Liddle, Rodger A.
通讯作者：
Liddle, Rodger A.