Multiple
sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis
(EAE), are inflammatory diseases of the central nervous system (CNS), mediated
by several immune cells. Oligodendrocytes are responsible for the formation
and maintenance of myelin around multiple axons. In MS oligodendrocytes are the targets of inflammatory and immune
attacks. Thus,
the destruction of a single oligodendrocyte, possibly by apoptosis, results in
the loss of myelin around several axons and the loss of many oligodendrocytes
limiting the ability to repair or regenerate demyelinated areas. Apoptosis is
mediated by an aggregation of various protein components, specifically death
domains (DD) superfamily. This superfamily is composed of the death domain
(DD), the death effector domain (DED), the caspase recruitment domain (CARD)
and the pyrin domain (PYD) subfamilies. Within each subfamily, members form
homotypic interactions and facilitate the assembly of oligomeric signaling complexes.
Members of the death domain superfamily are critical components of apoptotic
and inflammatory signaling. We summarize the structure and functions of the DD
superfamily, and describe the role of the DD proteins in oligodendrocytes death
and proinflammatory activation in MS pathogenesis.
Cite this paper
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