Molecular hallmarks of ageing in amyotrophic lateral sclerosis.
ALS
Ageing
Molecular hallmarks
Neurodegenerative diseases
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
02 Mar 2024
02 Mar 2024
Historique:
received:
05
12
2023
accepted:
06
02
2024
revised:
21
01
2024
medline:
2
3
2024
pubmed:
2
3
2024
entrez:
2
3
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38430277
doi: 10.1007/s00018-024-05164-9
pii: 10.1007/s00018-024-05164-9
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
111Subventions
Organisme : National Institute for Dementia Research
ID : 1095215
Organisme : Motor Neurone Disease Australia
ID : Peter Stearne Familial MND Research Grant
Organisme : Motor Neurone Disease Australia
ID : Linda Rynalski Bridge Funding Grant
Organisme : FightMND
ID : 51909/00
Informations de copyright
© 2024. The Author(s).
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