Decoding the relationship between ageing and amyotrophic lateral sclerosis: a cellular perspective.
Virenkumar A Pandya
Rickie Patani
10779/crick.12229116.v1
https://crick.figshare.com/articles/journal_contribution/Decoding_the_relationship_between_ageing_and_amyotrophic_lateral_sclerosis_a_cellular_perspective_/12229116
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.
2020-05-04 13:04:49
ageing
amyotrophic lateral sclerosis
healthspan
lower motor unit
neuromuscular junction
Patani - sec
Neurology & Neurosurgery
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences