Extracellular cues influencing oligodendrocyte differentiation and
(re)myelination
#MMPMID27016069
Wheeler NA
; Fuss B
Exp Neurol
2016[Sep]; 283
(Pt B
): 512-30
PMID27016069
show ga
There is an increasing number of neurologic disorders found to be associated with
loss and/or dysfunction of the CNS myelin sheath, ranging from the classic
demyelinating disease, multiple sclerosis, through CNS injury, to
neuropsychiatric diseases. The disabling burden of these diseases has sparked a
growing interest in gaining a better understanding of the molecular mechanisms
regulating the differentiation of the myelinating cells of the CNS,
oligodendrocytes (OLGs), and the process of (re)myelination. In this context, the
importance of the extracellular milieu is becoming increasingly recognized. Under
pathological conditions, changes in inhibitory as well as permissive/promotional
cues are thought to lead to an overall extracellular environment that is
obstructive for the regeneration of the myelin sheath. Given the general view
that remyelination is, even though limited in human, a natural response to
demyelination, targeting pathologically 'dysregulated' extracellular cues and
their downstream pathways is regarded as a promising approach toward the
enhancement of remyelination by endogenous (or if necessary transplanted) OLG
progenitor cells. In this review, we will introduce the extracellular cues that
have been implicated in the modulation of (re)myelination. These cues can be
soluble, part of the extracellular matrix (ECM) or mediators of cell-cell
interactions. Their inhibitory and permissive/promotional roles with regard to
remyelination as well as their potential for therapeutic intervention will be
discussed.
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