Journal article

Dysfunction in nonsense-mediated decay, protein homeostasis, mitochondrial function, and brain connectivity in ALS-FUS mice with cognitive deficits

Wan Yun Ho, Ira Agrawal, Sheue-Houy Tyan, Emma Sanford, Wei-Tang Chang, Kenneth Lim, Jolynn Ong, Bernice Siu Yan Tan, Aung Aung Kywe Moe, Regina Yu, Peiyan Wong, Greg Tucker-Kellogg, Edward Koo, Kai-Hsiang Chuang, Shuo-Chien Ling



Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of the same disease spectrum of adult-onset neurodegenerative diseases that affect the motor and cognitive functions, respectively. Multiple common genetic loci such as fused in sarcoma (FUS) have been identified to play a role in ALS and FTD etiology. Current studies indicate that FUS mutations incur gain-of-toxic functions to drive ALS pathogenesis. However, how the disease-linked mutations of FUS affect cognition remains elusive. Using a mouse model expressing an ALS-linked human FUS mutation (R514G-FUS) that mimics endogenous expression patterns, we found that FUS proteins showed an age-dependent acc..

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University of Melbourne Researchers


Awarded by National Medical Research Council

Awarded by Ministry of Education, Singapore

Funding Acknowledgements

This work was supported by grants to S.-C. L. from the Swee Liew-Wadsworth Endowment fund, National University of Singapore (NUS), National Medical Research Council (NMRC/OFIRG/0001/2016) and Ministry of Education (MOE2016-T2-1-024), Singapore.