TY - JOUR

T1 - Targeting senescence to delay progression of multiple sclerosis

AU - Oost, Wendy

AU - Talma, Nynke

AU - Meilof, Jan F

AU - Laman, Jon D

PY - 2018/11

Y1 - 2018/11

N2 - Multiple sclerosis (MS) is a chronic and often progressive, demyelinating disease of the central nervous system (CNS) white and gray matter and the single most common cause of disability in young adults. Age is one of the factors most strongly influencing the course of progression in MS. One of the hallmarks of aging is cellular senescence. The elimination of senescent cells with senolytics has very recently been shown to delay age-related dysfunction in animal models for other neurological diseases. In this review, the possible link between cellular senescence and the progression of MS is discussed, and the potential use of senolytics as a treatment for progressive MS is explored. Currently, there is no cure for MS and there are limited treatment options to slow the progression of MS. Current treatment is based on immunomodulatory approaches. Various cell types present in the CNS can become senescent and thus potentially contribute to MS disease progression. We propose that, after cellular senescence has indeed been shown to be directly implicated in disease progression, administration of senolytics should be tested as a potential therapeutic approach for the treatment of progressive MS.

AB - Multiple sclerosis (MS) is a chronic and often progressive, demyelinating disease of the central nervous system (CNS) white and gray matter and the single most common cause of disability in young adults. Age is one of the factors most strongly influencing the course of progression in MS. One of the hallmarks of aging is cellular senescence. The elimination of senescent cells with senolytics has very recently been shown to delay age-related dysfunction in animal models for other neurological diseases. In this review, the possible link between cellular senescence and the progression of MS is discussed, and the potential use of senolytics as a treatment for progressive MS is explored. Currently, there is no cure for MS and there are limited treatment options to slow the progression of MS. Current treatment is based on immunomodulatory approaches. Various cell types present in the CNS can become senescent and thus potentially contribute to MS disease progression. We propose that, after cellular senescence has indeed been shown to be directly implicated in disease progression, administration of senolytics should be tested as a potential therapeutic approach for the treatment of progressive MS.

KW - Aging

KW - Senolytics

KW - Glia

KW - Neurodegeneration

KW - Inflammation

KW - Autoimmunity

KW - CENTRAL-NERVOUS-SYSTEM

KW - VASCULAR ENDOTHELIAL-CELLS

KW - CD4(+)CD28(-) T-CELLS

KW - BLOOD-BRAIN-BARRIER

KW - CELLULAR SENESCENCE

KW - SECRETORY PHENOTYPE

KW - CNS REMYELINATION

KW - SENOLYTIC DRUGS

KW - PRECURSOR CELLS

KW - CANCER CELLS

U2 - 10.1007/s00109-018-1686-x

DO - 10.1007/s00109-018-1686-x

M3 - Review article

C2 - 30229272

VL - 96

SP - 1153

EP - 1166

JO - Journal of Molecular Medicine

JF - Journal of Molecular Medicine

SN - 0946-2716

IS - 11

ER -