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The genetic basis of amyotrophic lateral sclerosis: recent breakthroughs

Authors Eykens C, Robberecht W

Received 31 January 2015

Accepted for publication 30 March 2015

Published 5 October 2015 Volume 2015:5 Pages 327—345


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr John Martignetti

Caroline Eykens,1,2 Wim Robberecht1–3

1Research Group Experimental Neurology, Department of Neurosciences, KU Leuven – University of Leuven, Leuven, Belgium; 2Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium; 3Department of Neurology, University Hospitals Leuven, Leuven, Belgium

Abstract: Deciphering the genetic architecture of amyotrophic lateral sclerosis (ALS), an adult-onset neurodegenerative disorder of the motor neuron system, is important to understand the etiology of this fatal disease as well as to develop customized ALS therapies based on the patient's genetic fingerprint. In this review, we discuss the genetic basis of ALS, and attempt to link the causal genes to three highly interrelated pathogenic mechanisms: dysproteostasis, RNA dysregulation, and axon dysfunction. In addition, we address the clinical and biological implications of these genetic findings. Furthermore, we explore to what extent genetic knowledge can be converted into targeted and personalized treatments.

Keywords: amyotrophic lateral sclerosis, frontotemporal dementia, genetics, disease modifiers, personalized medicine

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