Abstract
Research onto the pathogenesis of amyotrophic lateral sclerosis (ALS) has obtained notable gene discoveries, although, to date, only progress with regard to treatment has been very modest. Currently ALS is considered a multifactorial disease that presents diverse clinical presentations, ranging from a monogenic inherited disease to an autoimmune pathology, and develops with misfolded protein aggregation and neuroinflammation. An important factor related to ALS pathogenesis is the microglial activation associated with degenerative motor neurons. This activation leads to changes in the expression of a wide range of genes related to phagocytosis and inflammation, and to profound modifications in the dynamic interactions between neurons and glial cells. Overactivation and deregulation of microglial activity causes deleterious effects and leads to neuronal death. However, the involvement of microglia in non-inflammatory functions challenges our concept of neuroinflammation and opens up new possibilities for the study of the pathophysiological mechanisms of ALS. In this review we summarize the current knowledge on the adaptive interactions between neurons and microglia in ALS. We also discuss the hypothesis that controlling the extent of microglial activation and neuroinflammation may have clinical and therapeutic benefits for the condition.
Keywords: Amyotrophic lateral sclerosis, motor neuron disease, neuroinflammation, microglia, astroglia, neuronglia interaction.
Current Medicinal Chemistry
Title:Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited
Volume: 23 Issue: 42
Author(s): Manuel J. Rodríguez and Nicole Mahy
Affiliation:
Keywords: Amyotrophic lateral sclerosis, motor neuron disease, neuroinflammation, microglia, astroglia, neuronglia interaction.
Abstract: Research onto the pathogenesis of amyotrophic lateral sclerosis (ALS) has obtained notable gene discoveries, although, to date, only progress with regard to treatment has been very modest. Currently ALS is considered a multifactorial disease that presents diverse clinical presentations, ranging from a monogenic inherited disease to an autoimmune pathology, and develops with misfolded protein aggregation and neuroinflammation. An important factor related to ALS pathogenesis is the microglial activation associated with degenerative motor neurons. This activation leads to changes in the expression of a wide range of genes related to phagocytosis and inflammation, and to profound modifications in the dynamic interactions between neurons and glial cells. Overactivation and deregulation of microglial activity causes deleterious effects and leads to neuronal death. However, the involvement of microglia in non-inflammatory functions challenges our concept of neuroinflammation and opens up new possibilities for the study of the pathophysiological mechanisms of ALS. In this review we summarize the current knowledge on the adaptive interactions between neurons and microglia in ALS. We also discuss the hypothesis that controlling the extent of microglial activation and neuroinflammation may have clinical and therapeutic benefits for the condition.
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Cite this article as:
Rodríguez J. Manuel and Mahy Nicole, Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited, Current Medicinal Chemistry 2016; 23 (42) . https://dx.doi.org/10.2174/0929867324666161123091314
DOI https://dx.doi.org/10.2174/0929867324666161123091314 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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