Is cellular senescence responsible for disability progression in progressive multiple sclerosis?
Description: Our understanding of the mechanisms that underlie the build-up of neurological deficit in the progressive forms of multiple sclerosis (MS) remains incomplete, which explains our current lack of treatments that can effectively prevent disability progression in these forms of the disease. Nevertheless, age-related processes may have a role as epidemiological evidence suggest that patient age is the most robust factor predicting the transition from RR-MS to SP-MS. Cellular senescence (CS) is a physiologic response that prevents the propagation of damaged cells. It is mainly characterized by cell cycle arrest combined with typical phenotypic changes including secretion of proinflammatory mediators. Several insults such as chronic inflammation and oxidative stress can induce senescence and the proportion of senescent cells in tissues increases with aging. Although CS has a thoroughly studied beneficial role in preventing damaged cells from becoming neoplastic, evidence indicates that accelerated CS might also contribute to loss of tissue function associated with aging and neurodegenerative disease. This project aims to test the hypothesis that age-dependent accumulation of senescent cells in chronic demyelinated MS lesions is at least partly responsible for the progressive loss of CNS function, which manifests as build-up of irreversible disability in the progressive forms of the disease.
Funder: Multiple Sclerosis Society
Amount: £40,000
Funding type: research
Funder scheme: Innovative grant application
Start date: 2018-05-14
End date: 2019-02-13
Investigators: Richard Nicholas, Richard Nicholas
Institution: Imperial College London
Funded outputs count: 0
Funder award ID: 75
OpenAlex ID: G9000485696