Role and Therapeutic Potential of Astrocytes in Amyotrophic Lateral Sclerosis

Author(s): Mariana Pehar, Benjamin A. Harlan, Kelby M. Killoy, Marcelo R. Vargas*.

Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 33 , 2017

Abstract:

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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Article Details

VOLUME: 23
ISSUE: 33
Year: 2017
Page: [5010 - 5021]
Pages: 12
DOI: 10.2174/1381612823666170622095802
Price: $58

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