Molecular hallmarks of ageing in amyotrophic lateral sclerosis

Research output: Contribution to journalReview articlepeer-review

21 Downloads (Pure)

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal, severely debilitating and rapidly progressing disorder affecting motor neurons in the brain, brainstem, and spinal cord. Unfortunately, there are few effective treatments, thus there remains a critical need to find novel interventions that can mitigate against its effects. Whilst the aetiology of ALS remains unclear, ageing is the major risk factor. Ageing is a slowly progressive process marked by functional decline of an organism over its lifespan. However, it remains unclear how ageing promotes the risk of ALS. At the molecular and cellular level there are specific hallmarks characteristic of normal ageing. These hallmarks are highly inter-related and overlap significantly with each other. Moreover, whilst ageing is a normal process, there are striking similarities at the molecular level between these factors and neurodegeneration in ALS. Nine ageing hallmarks were originally proposed: genomic instability, loss of telomeres, senescence, epigenetic modifications, dysregulated nutrient sensing, loss of proteostasis, mitochondrial dysfunction, stem cell exhaustion, and altered inter-cellular communication. However, these were recently (2023) expanded to include dysregulation of autophagy, inflammation and dysbiosis. Hence, given the latest updates to these hallmarks, and their close association to disease processes in ALS, a new examination of their relationship to pathophysiology is warranted. In this review, we describe possible mechanisms by which normal ageing impacts on neurodegenerative mechanisms implicated in ALS, and new therapeutic interventions that may arise from this.

Original languageEnglish
Article number111
Pages (from-to)1-30
Number of pages30
JournalCellular and Molecular Life Sciences
Volume81
Issue number1
DOIs
Publication statusPublished - 2 Mar 2024

Bibliographical note

Copyright the Author(s) 2024. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Ageing
  • ALS
  • Neurodegenerative diseases
  • Molecular hallmarks

Fingerprint

Dive into the research topics of 'Molecular hallmarks of ageing in amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

Cite this