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2015 ; 6
(ä): 180
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The Role of Astrocytes in Multiple Sclerosis Progression
#MMPMID26347709
Correale J
; Farez MF
Front Neurol
2015[]; 6
(ä): 180
PMID26347709
show ga
Multiple sclerosis (MS) is an inflammatory disorder causing central nervous
system (CNS) demyelination and axonal injury. Although its etiology remains
elusive, several lines of evidence support the concept that autoimmunity plays a
major role in disease pathogenesis. The course of MS is highly variable;
nevertheless, the majority of patients initially present a relapsing-remitting
clinical course. After 10-15?years of disease, this pattern becomes progressive
in up to 50% of untreated patients, during which time clinical symptoms slowly
cause constant deterioration over a period of many years. In about 15% of MS
patients, however, disease progression is relentless from disease onset.
Published evidence supports the concept that progressive MS reflects a poorly
understood mechanism of insidious axonal degeneration and neuronal loss.
Recently, the type of microglial cell and of astrocyte activation and
proliferation observed has suggested contribution of resident CNS cells may play
a critical role in disease progression. Astrocytes could contribute to this
process through several mechanisms: (a) as part of the innate immune system, (b)
as a source of cytotoxic factors, (c) inhibiting remyelination and axonal
regeneration by forming a glial scar, and (d) contributing to axonal
mitochondrial dysfunction. Furthermore, regulatory mechanisms mediated by
astrocytes can be affected by aging. Notably, astrocytes might also limit the
detrimental effects of pro-inflammatory factors, while providing support and
protection for oligodendrocytes and neurons. Because of the dichotomy observed in
astrocytic effects, the design of therapeutic strategies targeting astrocytes
becomes a challenging endeavor. Better knowledge of molecular and functional
properties of astrocytes, therefore, should promote understanding of their
specific role in MS pathophysiology, and consequently lead to development of
novel and more successful therapeutic approaches.
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