Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons
in the spinal cord, brain stem, and motor cortex. The molecular mechanism underlying the progressive degeneration
of motor neuron remains uncertain but involves a non-cell autonomous process. In acute injury or degenerative
diseases astrocytes adopt a reactive phenotype known as astrogliosis. Astrogliosis is a complex remodeling of
astrocyte biology and most likely represents a continuum of potential phenotypes that affect neuronal function
and survival in an injury-specific manner. In ALS patients, reactive astrocytes surround both upper and lower
degenerating motor neurons and play a key role in the pathology. It has become clear that astrocytes play a major
role in ALS pathology. Through loss of normal function or acquired new characteristics, astrocytes are able to
influence motor neuron fate and the progression of the disease. The use of different cell culture models indicates
that ALS-astrocytes are able to induce motor neuron death by secreting a soluble factor(s). Here, we discuss several
pathogenic mechanisms that have been proposed to explain astrocyte-mediated motor neuron death in ALS.
In addition, examples of strategies that revert astrocyte-mediated motor neuron toxicity are reviewed to illustrate
the therapeutic potential of astrocytes in ALS. Due to the central role played by astrocytes in ALS pathology,
therapies aimed at modulating astrocyte biology may contribute to the development of integral therapeutic approaches
to halt ALS progression.
Keywords: Astrocytes, gliosis, motor neuron, neurodegeneration, oxidative stress, amyotrophic lateral sclerosis.
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