Abstract
As the mechanisms underlying neuronal development and degeneration become clarified, a number of common effectors and signaling pathways are becoming apparent. Here we describe the identification of Abeta, long considered a pathologic mediator of Alzheimers Disease and Down Syndrome, as similarly over-expressed in the neurodevelopmental disease, Fragile X Syndrome. We also show that mGluR5 inhibitors, currently employed for the treatment of Fragile X, reduce Abeta production in rodent models of Fragile X and AD as well as reduce disease phenotypes including seizures. Thus seemingly disparate neurologic diseases may share a common pathologic instigator and be treatable with a common, currently available class of therapeutics.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Alzheimer Disease / drug therapy
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Alzheimer Disease / metabolism*
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / antagonists & inhibitors
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Amyloid beta-Peptides / biosynthesis*
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Amyloid beta-Peptides / genetics
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism*
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Animals
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Brain / drug effects
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Brain / metabolism
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Brain / physiopathology
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Disease Models, Animal
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Amino Acid Antagonists / therapeutic use
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Fragile X Mental Retardation Protein / genetics
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Fragile X Syndrome / drug therapy
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Fragile X Syndrome / metabolism*
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Fragile X Syndrome / physiopathology
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Glutamic Acid / metabolism
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Humans
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Phenotype
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate / antagonists & inhibitors
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Receptors, Metabotropic Glutamate / metabolism*
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Excitatory Amino Acid Antagonists
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GRM5 protein, human
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Receptor, Metabotropic Glutamate 5
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Receptors, Metabotropic Glutamate
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Fragile X Mental Retardation Protein
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Glutamic Acid