The neuroprotective KDI domain of gamma 1-laminin is a universal and potent inhibitor of ionotropic glutamate receptors.
Previous work from this laboratory indicates that the KDI (Lys-Asp-Ile) domain of gamma 1-laminin promotes functional regeneration of adult rat spinal cord injuries and protects adult rat hippocampal neurons against massive neuronal death induced by intracerebral injection of the glutamate analogue kainic acid. In the present study, we used patch clamp recordings on cultured human embryonic neocortical neurons and HEK 293 cells expressing recombinant glutamate receptor subunits to study a putative interaction of the KDI with the glutamate system. We show that the KDI domain of gamma 1-laminin is a universal and potent inhibitor of AMPA, kainate, and NMDA subclasses of glutamate receptors, with a noncompetitive action on the AMPA receptor channel activity. Glutamate neurotoxicity plays a key role in both CNS trauma and neurodegenerative disorders, so this unexpected, novel function of the gamma 1-laminin-derived tripeptide may prove clinically valuable in treatment of CNS trauma and/or disease.
Möykkynen
Tommi
T
Institute of Biomedicine (Pharmacology), Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Liebkind
Ron
R
Sjöberg
Jari
J
Korpi
Esa R
ER
Liesi
Päivi
P
D002460:Cell Line; D002478:Cells, Cultured; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D007797:Laminin; D018696:Neuroprotective Agents; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C089141:laminin gamma 1