C9orf72 loss-of-function: a trivial, stand-alone or additive mechanism in C9 ALS/FTD?
C9orf72 loss-of-function: a trivial, stand-alone or additive mechanism in C9 ALS/FTD?
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DOI：
10.1007/s00401-020-02214-x
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发表时间：
2020-11
影响因子：
12.7
通讯作者：
Van Den Bosch L
中科院分区：
文献类型：
--
作者：
Braems E;Swinnen B;Van Den Bosch L
A repeat expansion in C9orf72 is responsible for the characteristic neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in a still unresolved manner. Proposed mechanisms involve gain-of-functions, comprising RNA and protein toxicity, and loss-of-function of the C9orf72 gene. Their exact contribution is still inconclusive and reports regarding loss-of-function are rather inconsistent. Here, we review the function of the C9orf72 protein and its relevance in disease. We explore the potential link between reduced C9orf72 levels and disease phenotypes in postmortem, in vitro, and in vivo models. Moreover, the significance of loss-of-function in other non-coding repeat expansion diseases is used to clarify its contribution in C9orf72 ALS/FTD. In conclusion, with evidence pointing to a multiple-hit model, loss-of-function on itself seems to be insufficient to cause neurodegeneration in C9orf72 ALS/FTD.
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影响因子：
17.1
作者：
Burberry A;Suzuki N;Wang JY;Moccia R;Mordes DA;Stewart MH;Suzuki-Uematsu S;Ghosh S;Singh A;Merkle FT;Koszka K;Li QZ;Zon L;Rossi DJ;Trowbridge JJ;Notarangelo LD;Eggan K
通讯作者：
Eggan K
影响因子：
12.7
作者：
Cooper-Knock J;Higginbottom A;Stopford MJ;Highley JR;Ince PG;Wharton SB;Pickering-Brown S;Kirby J;Hautbergue GM;Shaw PJ
通讯作者：
Shaw PJ
影响因子：
9.2
作者：
Corrionero, Anna;Horvitz, H. Robert
通讯作者：
Horvitz, H. Robert
C9ORF72和P62的复合物使用精氨酸甲基化来消除自噬的应激颗粒。
影响因子：
16.6
作者：
Chitiprolu M;Jagow C;Tremblay V;Bondy-Chorney E;Paris G;Savard A;Palidwor G;Barry FA;Zinman L;Keith J;Rogaeva E;Robertson J;Lavallée-Adam M;Woulfe J;Couture JF;Côté J;Gibbings D
通讯作者：
Gibbings D
影响因子：
3.3
作者：
Amick J;Roczniak-Ferguson A;Ferguson SM
通讯作者：
Ferguson SM