期刊
BRAIN
卷 143, 期 -, 页码 1057-1072出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awz360
关键词
amyotrophic lateral sclerosis; ageing; neuromuscular junction; lower motor unit; healthspan
资金
- Rosetrees Trust [548644]
- University College London MBPhD Programme
- MRC Senior Clinical Fellowship [MR/S006591/1]
- MRC [MR/S006591/1] Funding Source: UKRI
With an ageing population comes an inevitable increase in the prevalence of age-associated neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), a relentlessly progressive and universally fatal disease characterized by the degeneration of upper and lower motor neurons within the brain and spinal cord. Indeed, the physiological process of ageing causes a variety of molecular and cellular phenotypes. With dysfunction at the neuromuscular junction implicated as a key pathological mechanism in ALS, and each lower motor unit cell type vulnerable to its own set of age-related phenotypes, the effects of ageing might in fact prove a prerequisite to ALS, rendering the cells susceptible to disease-specific mechanisms. Moreover, we discuss evidence for overlap between age and ALS-associated hallmarks, potentially implicating cell type-specific ageing as a key contributor to this multifactorial and complex disease. With a dearth of disease-modifying therapy currently available for ALS patients and a substantial failure in bench to bedside translation of other potential therapies, the unification of research in ageing and ALS requires high fidelity models to better recapitulate age-related human disease and will ultimately yield more reliable candidate therapeutics for patients, with the aim of enhancing healthspan and life expectancy.
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