Converging pathways in neurodegeneration, from genetics to mechanisms.
Converging pathways in neurodegeneration, from genetics to mechanisms.
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DOI：
10.1038/s41593-018-0237-7
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发表时间：
2018-10
影响因子：
25
通讯作者：
La Spada AR
中科院分区：
文献类型：
--
作者：
Gan L;Cookson MR;Petrucelli L;La Spada AR
神经退行性疾病导致认知和/或运动功能的进行性丧失，并对人口迅速老龄化的社会构成重大挑战。人类遗传学研究表明，致病的罕见突变和风险相关的常见等位基因在不同的神经退行性疾病中重叠。在这里，我们回顾了复杂的基因型-表型关系和常见的细胞通路出现在最近的遗传和机制的研究。共同的病理机制包括有缺陷的蛋白质质量控制和降解途径，功能失调的线粒体稳态，应激颗粒和适应不良的先天免疫反应。最近的治疗成功和令人鼓舞的治疗前景表明，研究工作已开始取得成果。
Neurodegenerative diseases cause progressive loss of cognitive and/or motor function and pose major challenges for societies with rapidly aging populations. Human genetics studies have shown that disease-causing rare mutations and risk-associated common alleles overlap in different neurodegenerative disorders. Here we review the intricate genotype-phenotype relationships and common cellular pathways emerging from recent genetic and mechanistic studies. Shared pathological mechanisms include defective protein quality-control and degradation pathways, dysfunctional mitochondrial homeostasis, stress granules, and maladaptive innate immune responses. Research efforts have started to bear fruit, as shown by recent treatment successes and an encouraging therapeutic outlook.
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DOI：
10.1126/science.aaa3650
发表时间：
2015-03-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cirulli ET;Lasseigne BN;Petrovski S;Sapp PC;Dion PA;Leblond CS;Couthouis J;Lu YF;Wang Q;Krueger BJ;Ren Z;Keebler J;Han Y;Levy SE;Boone BE;Wimbish JR;Waite LL;Jones AL;Carulli JP;Day-Williams AG;Staropoli JF;Xin WW;Chesi A;Raphael AR;McKenna-Yasek D;Cady J;Vianney de Jong JM;Kenna KP;Smith BN;Topp S;Miller J;Gkazi A;FALS Sequencing Consortium;Al-Chalabi A;van den Berg LH;Veldink J;Silani V;Ticozzi N;Shaw CE;Baloh RH;Appel S;Simpson E;Lagier-Tourenne C;Pulst SM;Gibson S;Trojanowski JQ;Elman L;McCluskey L;Grossman M;Shneider NA;Chung WK;Ravits JM;Glass JD;Sims KB;Van Deerlin VM;Maniatis T;Hayes SD;Ordureau A;Swarup S;Landers J;Baas F;Allen AS;Bedlack RS;Harper JW;Gitler AD;Rouleau GA;Brown R;Harms MB;Cooper GM;Harris T;Myers RM;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
3.5
作者：
Bras J;Guerreiro R;Darwent L;Parkkinen L;Ansorge O;Escott-Price V;Hernandez DG;Nalls MA;Clark LN;Honig LS;Marder K;Van Der Flier WM;Lemstra A;Scheltens P;Rogaeva E;St George-Hyslop P;Londos E;Zetterberg H;Ortega-Cubero S;Pastor P;Ferman TJ;Graff-Radford NR;Ross OA;Barber I;Braae A;Brown K;Morgan K;Maetzler W;Berg D;Troakes C;Al-Sarraj S;Lashley T;Compta Y;Revesz T;Lees A;Cairns N;Halliday GM;Mann D;Pickering-Brown S;Dickson DW;Singleton A;Hardy J
通讯作者：
Hardy J
影响因子：
9.3
作者：
Cribbs DH;Berchtold NC;Perreau V;Coleman PD;Rogers J;Tenner AJ;Cotman CW
通讯作者：
Cotman CW
DOI：
10.1126/science.aam9080
发表时间：
2017-09-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Burbulla LF;Song P;Mazzulli JR;Zampese E;Wong YC;Jeon S;Santos DP;Blanz J;Obermaier CD;Strojny C;Savas JN;Kiskinis E;Zhuang X;Krüger R;Surmeier DJ;Krainc D
通讯作者：
Krainc D
影响因子：
30.8
作者：
Chang D;Nalls MA;Hallgrímsdóttir IB;Hunkapiller J;van der Brug M;Cai F;International Parkinson's Disease Genomics Consortium;23andMe Research Team;Kerchner GA;Ayalon G;Bingol B;Sheng M;Hinds D;Behrens TW;Singleton AB;Bhangale TR;Graham RR
通讯作者：
Graham RR