Gene

microRNA

Amyotrophic lateral sclerosis

Neuroscience

Biology

Messenger RNA

C9orf72

RNA-binding protein

Motor neuron

Immunology

Genetics

Trinucleotide repeat expansion

Spinal cord

RNA splicing

Alternative splicing

TARDBP

Medicine

Allele

SOD1

Disease

Pathogenesis

Pathology

Frontiers in Genetics

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease and is characterized by the degeneration of upper and lower motor neurons. It has become increasingly clear that RNA dysregulation is a key contributor to ALS pathogenesis. The major ALS genes SOD1, TARDBP, FUS, and C9orf72 are involved in aspects of RNA metabolism processes such as mRNA transcription, alternative splicing, RNA transport, mRNA stabilization, and miRNA biogenesis. In this review, we highlight the current understanding of RNA dysregulation in ALS pathogenesis involving these major ALS genes and discuss the potential of therapeutic strategies targeting disease RNAs for treating ALS.

RNA Dysregulation in Amyotrophic Lateral Sclerosis