Abstract
Microglial activation is thought to contribute to the progression of selective motor neuron death during amyotrophic lateral sclerosis (ALS). As minocycline has been shown to inhibit microglial activation, the therapeutic efficacy of this tetracycline derivative in the G93A mice model for familial ALS was tested. This drug with proven safety delayed disease onset and dose-dependently extended the survival of the G93A mice. At 120 days of age, minocycline protected mice from loss of motor neurons and from vacuolization. These results demonstrate that interference with immuno-inflammatory responses has a beneficial effect in the ALS mice model, suggesting this to be a potential new strategy to treat ALS.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Age Factors
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Amyotrophic Lateral Sclerosis / drug therapy*
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Amyotrophic Lateral Sclerosis / immunology
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Amyotrophic Lateral Sclerosis / mortality
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Animals
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Anti-Bacterial Agents / pharmacology*
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Anti-Bacterial Agents / therapeutic use
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Cell Survival / drug effects
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Cell Survival / physiology
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Disease Models, Animal
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Disease Progression
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Dose-Response Relationship, Drug
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Female
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Inflammation / drug therapy
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Inflammation / immunology
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Inflammation / mortality
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Male
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Mice
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Mice, Transgenic
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Microglia / drug effects*
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Microglia / immunology
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Microglia / metabolism
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Minocycline / pharmacology*
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Minocycline / therapeutic use
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Motor Activity / drug effects
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Motor Activity / physiology
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Motor Neurons / drug effects*
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Motor Neurons / immunology
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Motor Neurons / pathology
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Neuroprotective Agents / pharmacology*
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Neuroprotective Agents / therapeutic use
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Spinal Cord / drug effects*
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Spinal Cord / immunology
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Spinal Cord / pathology
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Survival Rate
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Treatment Outcome
Substances
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Anti-Bacterial Agents
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Neuroprotective Agents
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Minocycline