Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease.
Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease.
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DOI：
10.1016/j.nbd.2018.03.008
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发表时间：
2019-03
影响因子：
6.1
通讯作者：
Mazzulli JR
中科院分区：
文献类型：
--
作者：
Pitcairn C;Wani WY;Mazzulli JR
戈谢病（GD）基因GBA 1突变是帕金森病（PD）的一个强风险因素，这一发现使人们对以自噬-溶酶体通路破坏为中心的病理生理学有了独特的见解。路易体形式的蛋白质聚集和聚集在溶酶体降解系统上的典型PD突变的影响表明，PD中的神经变性是由蛋白质稳态失调介导的。PD和溶酶体储积症GD之间的良好临床和病理关系强调了蛋白质代谢失调在神经退行性变中的重要性，这种关系的一个有趣部分是这两种疾病中自噬-溶酶体功能障碍的共同表型。这些发现的转化应用可以通过使用源自诱导多能干细胞（iPSC）的中脑多巴胺神经元模型来加速，所述诱导多能干细胞概括GD和PD的若干病理特征。在这篇综述中，我们讨论了自噬功能障碍与GD和GBA 1相关帕金森病的病理生理学相关的证据，并更具体地关注最近在iPSC衍生神经元中进行的研究。
The finding that mutations in the Gaucher’s Disease (GD) gene GBA1 are a strong risk factor for Parkinson’s Disease (PD) has allowed for unique insights into pathophysiology centered on disruption of the autophagic-lysosomal pathway. Protein aggregations in the form of Lewy bodies and the effects of canonical PD mutations that converge on the lysosomal degradation system suggest that neurodegeneration in PD is mediated by dysregulation of protein homeostasis. The well-characterized clinical and pathological relationship between PD and the lysosomal storage disorder GD emphasizes the importance of dysregulated protein metabolism in neurodegeneration, and one intriguing piece of this relationship is a shared phenotype of autophagic-lysosomal dysfunction in both diseases. Translational application of these findings may be accelerated by the use of midbrain dopamine neuronal models derived from induced pluripotent stem cells (iPSCs) that recapitulate several pathological features of GD and PD. In this review, we discuss evidence linking autophagic dysfunction to the pathophysiology of GD and GBA1-linked parkinsonism and focus more specifically on studies performed recently in iPSC-derived neurons.
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影响因子：
17.1
作者：
Cooper O;Seo H;Andrabi S;Guardia-Laguarta C;Graziotto J;Sundberg M;McLean JR;Carrillo-Reid L;Xie Z;Osborn T;Hargus G;Deleidi M;Lawson T;Bogetofte H;Perez-Torres E;Clark L;Moskowitz C;Mazzulli J;Chen L;Volpicelli-Daley L;Romero N;Jiang H;Uitti RJ;Huang Z;Opala G;Scarffe LA;Dawson VL;Klein C;Feng J;Ross OA;Trojanowski JQ;Lee VM;Marder K;Surmeier DJ;Wszolek ZK;Przedborski S;Krainc D;Dawson TM;Isacson O
通讯作者：
Isacson O
影响因子：
2.3
作者：
Bendikov-Bar, Inna;Maor, Gali;Filocamo, Mirella;Horowitz, Mia
通讯作者：
Horowitz, Mia
影响因子：
3.9
作者：
BASU, A;GLEW, RH;HUTERER, S
通讯作者：
HUTERER, S
影响因子：
7.8
作者：
Aflaki E;Moaven N;Borger DK;Lopez G;Westbroek W;Chae JJ;Marugan J;Patnaik S;Maniwang E;Gonzalez AN;Sidransky E
通讯作者：
Sidransky E
影响因子：
56.9
作者：
BEUTLER, E
通讯作者：
BEUTLER, E