Astrogliosis in amyotrophic lateral sclerosis: role and therapeutic potential of astrocytes.
Amyotrophic lateral sclerosis (ALS) is a fatal disorder characterized by the progressive loss of motor neurons. Although the molecular mechanism underlying motor neuron degeneration remains unknown; non-neuronal cells (including astrocytes) shape motor neuron survival in ALS. Astrocytes closely interact with neurons to provide an optimized environment for neuronal function and respond to all forms of injury in a typical manner known as reactive astrogliosis. A strong reactive astrogliosis surrounds degenerating motor neurons in ALS patients and ALS-animal models. Although reactive astrogliosis in ALS is probably both primary and secondary to motor neuron degeneration; astrocytes are not passive observers and they can influence motor neuron fate. Due to the important functions that astrocytes perform in the central nervous system; it is of key importance to understand how these functions are altered when astrocytes become reactive in ALS. Here; we review the current evidences supporting a potential toxic role of astrocytes and their viability as therapeutic targets to alter motor neuron degeneration in ALS.
Vargas
Marcelo R
MR
Division of Pharmaceutical Sciences, University of Wisconsin, Madison, Wisconsin 53705, USA.
Johnson
Jeffrey A
JA
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D006801:Humans; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D053218:Receptors, Death Domain; C000606290:SOD1 protein, human; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1