Abstract
Autoantibodies to brain proteins are present in Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease) patients and in the Cln3-/- mouse model of this disease, suggesting an autoimmune component to pathogenesis. Using genetic or pharmaceutical approaches to attenuate this immune response in Cln3-/- mice, we demonstrate decreased neuroinflammation, decreased deposition of immunoglobulin G in the brain and protection of vulnerable neuron populations. Moreover, immune suppression results in a significant improvement in motor performance providing for the first plausible therapeutic approach for juvenile Batten disease.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoantibodies / drug effects
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Autoantibodies / immunology
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Blotting, Western
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Brain / drug effects*
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Brain / pathology
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Cell Count
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Disease Models, Animal
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Immunohistochemistry
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Immunosuppression Therapy*
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Immunosuppressive Agents / pharmacology*
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Male
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Membrane Glycoproteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Chaperones / genetics
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Motor Skills / drug effects
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Mycophenolic Acid / analogs & derivatives
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Mycophenolic Acid / pharmacology
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Neuronal Ceroid-Lipofuscinoses / drug therapy*
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Neuronal Ceroid-Lipofuscinoses / immunology*
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Neuronal Ceroid-Lipofuscinoses / pathology
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Neurons / drug effects
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Neurons / pathology
Substances
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Autoantibodies
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CLN3 protein, mouse
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Immunosuppressive Agents
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Membrane Glycoproteins
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Molecular Chaperones
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Mycophenolic Acid