The genetic basis of amyotrophic lateral sclerosis: recent breakthroughs

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.