Ageing as a risk factor for ALS/FTD

Hum Mol Genet. 2017 Oct 1;26(R2):R105-R113. doi: 10.1093/hmg/ddx247.

Abstract

Like many other neurodegenerative diseases, age is a major risk factor in the development of ALS/FTD. But why is this the case? Recent genetic advances have highlighted some of pathways involved in the development of disease, and, strikingly, they appear to substantially overlap with those known to directly modulate the ageing process. Many ALS/FTD linked genes play a direct role in autophagy/lysosomal degradation, one of the most important pathways linked to ageing. However, systemic processes such as inflammation, as well as cellular maintenance pathways, including RNA splicing and nuclear-cytoplasmic transport have been increasingly linked both to disease and ageing. We highlight some of the shared mechanisms between the ageing process itself and emerging pathogenic mechanisms in ALS/FTD.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / genetics
  • Aging / genetics
  • Aging / physiology
  • Amyotrophic Lateral Sclerosis / complications
  • Amyotrophic Lateral Sclerosis / genetics*
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Autophagy / genetics
  • DNA-Binding Proteins / genetics
  • Frontotemporal Dementia / genetics*
  • Frontotemporal Dementia / physiopathology*
  • Humans
  • Inflammation / metabolism
  • Lysosomes / metabolism
  • Mutation
  • RNA Splicing / genetics
  • Risk Factors

Substances

  • DNA-Binding Proteins