Article
Haploinsufficiency leads to neurodegeneration in C9ORF72 ALS/FTD human induced motor neurons.
Nature medicine - 1 Mar 2018
Shi Yingxiao, Lin Shaoyu, Staats Kim A, Li Yichen, Chang Wen-Hsuan, Hung Shu-Ting, Hendricks Eric, Linares Gabriel R, Wang Yaoming, Son Esther Y, Wen Xinmei, Kisler Kassandra, Wilkinson Brent, Menendez Louise, Sugawara Tohru, Woolwine Phillip, Huang Mickey, Cowan Michael J, Ge Brandon, Koutsodendris Nicole, Sandor Kaitlin P, Komberg Jacob, Vangoor Vamshidhar R, Senthilkumar Ketharini, Hennes Valerie, Seah Carina, Nelson Amy R, Cheng Tze-Yuan, Lee Shih-Jong J, August Paul R, Chen Jason A, Wisniewski Nicholas, Hanson-Smith Victor, Belgard T Grant, Zhang Alice, Coba Marcelo, Grunseich Chris, Ward Michael E, van den Berg Leonard H, Pasterkamp R Jeroen, Trotti Davide, Zlokovic Berislav V, Ichida Justin K
Abstract excerpt
An intronic GGGGCC repeat expansion in C9ORF72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but the pathogenic mechanism of this repeat remains unclear. Using human induced motor neurons (iMNs), we found that repeat-expanded C9ORF72 was haploinsufficient in ALS. We found that C9ORF72 interacted with endosomes and was required for normal vesicle trafficking and...
Topics
- Amyotrophic Lateral Sclerosis
- Animals
- C9orf72 Protein
- DNA Repeat Expansion
- Disease Models, Animal
- Endosomes