INT250253

Context Info Confidence 0.30 First Reported 2008 Last Reported 2008 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 4 Disease Relevance 2.95 Pain Relevance 1.09

plasma membrane (AQP4, SLC1A2) transmembrane transport (AQP4, SLC1A2) transport (AQP4) cytoplasm (AQP4)

Anatomy Link Frequency plasma 1 astrocytes 1 AQP4 (Homo sapiens) SLC1A2 (Homo sapiens)

Pain Link Frequency Relevance Heat Glutamate 216 99.74 Spinal cord 60 99.72 Central nervous system 84 98.96 Inflammation 28 94.76 Glutamate receptor 16 91.08 Multiple sclerosis 32 86.96 Demyelination 8 62.44 anesthesia 4 37.68 excitatory amino acid 8 5.00 Inflammatory response 4 5.00

Disease Link Frequency Relevance Heat Neuromyelitis Optica 348 99.16 Disease Progression 4 96.04 INFLAMMATION 32 94.76 Toxicity 20 94.32 Demyelinating Disease 60 93.80 Neurodegenerative Disease 12 92.88 Pressure And Volume Under Development 8 83.08 Autoimmune Disease 12 33.76 Targeted Disruption 12 29.52 Necrosis 4 5.00

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Event

Anatomy

Negation

Speculation

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Disease term

Our immunohistochemical analysis of nonpathologic human CNS tissue (both cortical and spinal cord) reveal that EAAT2, but not EAAT1, normally colocalizes with AQP4 in gray matter astrocytes (Fig. 5 A) and that EAAT2 is most enriched in spinal cord gray matter (Fig. 5 B, top).

AQP4 Binding (colocalizes) of EAAT2 in astrocytes associated with central nervous system and spinal cord

1) Confidence 0.30 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2571922 Disease Relevance 0.43 Pain Relevance 0.34

These results imply a specific association between AQP4 and EAAT2 that does not exist for EAAT1.

AQP4 Binding (association) of EAAT2

2) Confidence 0.29 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2571922 Disease Relevance 0.68 Pain Relevance 0.08

The reduction in astrocytic glutamate transport accompanying AQP4 down-regulation after exposure to NMO-IgG further supports our suggestion that AQP4 and EAAT2 are associated functionally in the plasma membrane.

AQP4 Binding (associated) of EAAT2 in plasma associated with neuromyelitis optica and glutamate

3) Confidence 0.29 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2571922 Disease Relevance 0.57 Pain Relevance 0.08

However, our demonstration that the major astrocytic glutamate transporter EAAT2 exists in a macromolecular complex with the AQP4 water channel, and is down-regulated by AQP4-specific autoantibodies that are restricted to patients with the NMO-spectrum of CNS inflammatory autoimmune demyelinating disorders, has unanticipated pathogenic implications for glutamate toxicity as a central mechanism in a spectrum of disorders that are commonly mistaken for MS.

AQP4 Binding (complex) of EAAT2 associated with toxicity, neuromyelitis optica, multiple sclerosis, glutamate, inflammation, central nervous system and demyelinating disease

4) Confidence 0.26 Published 2008 Journal The Journal of Experimental Medicine Section Body Doc Link PMC2571922 Disease Relevance 1.27 Pain Relevance 0.58

General Comments

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