The Role of Non-Coding RNAs in ALS

Genes (Basel). 2025 May 23;16(6):623. doi: 10.3390/genes16060623.

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, leading to muscle weakness, paralysis, and eventually death. The pathogenesis of ALS is influenced by genetic factors, environmental factors, and age-related dysfunctions. These factors, taken together, are responsible for sporadic cases of ALS, which account for approximately 85-90% of ALS cases, while familial ALS accounts for the remaining 10-15% of cases, usually with dominant traits. Despite advances in understanding and studying the disease, the cause of the onset of ALS remains unknown. Emerging evidence suggests that non-coding RNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play crucial roles in the pathogenesis of the disease. An abnormal expression of these molecules is implicated in various ALS-related processes, including motor neuron survival, protein aggregation, and inflammation. Here, we describe the dysregulation of non-coding RNAs in the pathogenic mechanism of ALS, highlighting the potential roles of miRNAs, lncRNAs, and circRNAs as biomarkers or therapeutic targets to examine the progression of the disease.

Keywords: amyotrophic lateral sclerosis (ALS); microRNAs; neurodegenerative disease; non-coding RNAs.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis* / genetics
  • Amyotrophic Lateral Sclerosis* / pathology
  • Animals
  • Biomarkers / metabolism
  • Humans
  • MicroRNAs* / genetics
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • RNA, Circular* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Untranslated* / genetics

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • RNA, Circular
  • RNA, Untranslated
  • Biomarkers