Kainic acid: insights from a neurotoxin into the pathophysiology of Huntington's disease.
Kainic acid, a conformationally restricted analog of L-glutamic acid, is a potent neuroexcitant. Consistent with the excitotoxin hypothesis of Olney, intrastriatal injection of kainic acid causes degeneration of neurons with perikarya within the striatum but spares axons passing through or terminating in the region. The striatal kainate lesion shares many neurochemical and histopathologic alterations with those observed in the hereditary neurodegenerative disorder of man, Huntington's Disease. Recent studies on the mechanism of neurotoxicity of kainate indicate that its action is complex and indirect; however, ligand binding studies have revealed specific receptors for kainate. Understanding the fundamental mechanisms involved in excitotoxin action may shed light on the pathophysiology of neurodegenerative disorders such as Huntington's Disease.
D000818:Animals; D001224:Aspartic Acid / Q000502:physiology; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects; D004195:Disease Models, Animal; D005971:Glutamates / Q000494:pharmacology / Q000502:physiology; D018698:Glutamic Acid; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission / Q000187:drug effects
D001224:Aspartic Acid; D005971:Glutamates; D018698:Glutamic Acid; D007608:Kainic Acid; D018377:Neurotransmitter Agents; D011759:Pyrrolidines; D011956:Receptors, Cell Surface; D018092:Kainic Acid Receptors