Possible role of receptor heteromers in multiple sclerosis.
Recent results suggest that cytokine and glutamate receptors can interact directly and form receptor heteromers. Due to such heteromers, cytokines can act not only as classical neuromediators but also directly enhance glutamate gated ion channel activity via allosteric mechanisms. Our opinion is that such heteromers may lead to enhanced glutamate neurotoxicity in pathogenic processes of multiple sclerosis. Thus, agents targeting evolutionary conserved leucine-rich motifs responsible for such dimerization of receptors may represent a useful strategy to inhibit excitotoxicity in multiple sclerosis.
Tarakanov
A O
AO
St. Petersburg Institute for Informatics and Automation, Russian Academy of Sciences, St. Petersburg, Russia. tar@iias.spb.su
Fuxe
K G
KG
Agnati
L F
LF
Goncharova
L B
LB
D000818:Animals; D018698:Glutamic Acid / Q000633:toxicity; D006801:Humans; D017628:Microglia / Q000502:physiology; D008959:Models, Neurological; D009103:Multiple Sclerosis / Q000503:physiopathology*; D055503:Protein Multimerization; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism*
D018121:Receptors, Cytokine; D017470:Receptors, Glutamate; D018698:Glutamic Acid