The Ambivalent Role of Apoptosis in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

Author(s): Holger M. Reichardt, Fred Luhder.

Journal Name: Current Pharmaceutical Design

Volume 18 , Issue 29 , 2012

Abstract:

Apoptosis is synonymous to programmed cell death, which occurs in response to a plethora of stimuli and employs a series of highly conserved mediators and pathways. Its ambivalent role in immunology is illustrated by the fact that this process not only serves homeostatic functions but also exerts harmful effects including tissue damage. This is particularly true for neuroinflammatory diseases such as multiple sclerosis (MS), the most frequent neurological disease to afflict adolescents in the western world. Considerable insight into the role of apoptosis in MS has been obtained by using its animal model experimental autoimmune encephalomyelitis (EAE). Experiments using the EAE model have revealed that cell death affects both infiltrating lymphocytes and CNS resident cells, and that it contributes to axonal injury as well as the resolution of inflammation. Furthermore, it was discovered that the molecules involved in inducing and regulating this process are the Fas-FasL system, pro- and anti-apoptotic Bcl-2 family members, ‘initiator’ and ‘effector’ caspases, glucocorticoid hormones and various modulatory proteins. The variety of apoptotic mechanisms in combination with their often opposing effects on the disease course highlights the need for a detailed understanding of apoptosis in this context. In the future, this may pave the way to novel approaches aiming at interfering with the apoptotic process to prevent tissue damage or at intentionally inducing cell death in order to ameliorate the disease by deleting autoreactive lymphocytes.

Keywords: Apoptosis, Bcl-2, Fas, glucocorticoid, caspase, EAE, MS, leukocyte, oligodendrocyte, lymphocytes.

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Article Details

VOLUME: 18
ISSUE: 29
Year: 2012
Page: [4453 - 4464]
Pages: 12
DOI: 10.2174/138161212802502224
Price: $58

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