Abstract
Recent advances in sequencing technologies and collaborative efforts have led to substantial progress in identifying the genetic causes of amyotrophic lateral sclerosis (ALS). This momentum has, in turn, fostered the development of putative molecular therapies. In this Review, we outline the current genetic knowledge, emphasizing recent discoveries and emerging concepts such as the implication of distinct types of mutation, variability in mutated genes in diverse genetic ancestries and gene-environment interactions. We also propose a high-level model to synthesize the interdependent effects of genetics, environmental and lifestyle factors, and ageing into a unified theory of ALS. Furthermore, we summarize the current status of therapies developed on the basis of genetic knowledge established for ALS over the past 30 years, and we discuss how developing treatments for ALS will advance our understanding of targeting other neurological diseases.
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