A semisynthetic glycosphingolipid (LIGA20) reduces 2,4, 5-trihydroxyphenylalanine neurotoxicity in primary neuronal cultures.
The semisynthetic glycosphingolipid derivative II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-chloro-acetamid e-4-trans- octadacene (LIGA20) attenuated injury induced by the excitotoxic L-dopa metabolite 2,4,5-trihydroxyphenylalanine (TOPA) in cultures of rat cerebellar granule cells when presented simultaneously with TOPA (EC50; 9 microM LIGA20). The natural glycosphingolipid ganglioside GM1 up to 200 microM was not neuroprotective as cotreatment, although pretreatment of cells for 2 h was efficacious. This greater potency and speed of LIGA20 action extended to limiting TOPA-induced death of cultured mesencephalic dopaminergic neurons. These data suggest that LIGA20 may have therapeutic potential for the treatment of disorders associated with excitotoxic processes.
Skaper
S D
SD
Fidia Research Laboratories, Abano Terme, Italy.
Fadda
E
E
Facci
L
L
Manev
H
H
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000633:toxicity; D005677:G(M1) Ganglioside / Q000494:pharmacology / Q000031:analogs & derivatives; D006028:Glycosphingolipids / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010300:Parkinson Disease / Q000188:drug therapy; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D006028:Glycosphingolipids; C086919:LIGA 20; C001388:6-hydroxydopa; D005677:G(M1) Ganglioside; D004295:Dihydroxyphenylalanine; D013110:Sphingosine