title: N(epsilon)-(gamma-L-glutamyl)-L-lysine (GGEL) is increased in cerebrospinal fluid of patients with Huntington's disease.
abstract: Pathological-length polyglutamine (Q(n)) expansions, such as those that occur in the huntingtin protein (htt) in Huntington's disease (HD), are excellent substrates for tissue transglutaminase in vitro, and transglutaminase activity is increased in post-mortem HD brain. However, direct evidence for the participation of tissue transglutaminase (or other transglutaminases) in HD patients in vivo is scarce. We now report that levels of N(epsilon)-(gamma-L-glutamyl)-L-lysine (GGEL)--a 'marker' isodipeptide produced by the transglutaminase reaction--are elevated in the CSF of HD patients (708 +/- 41 pmol/mL, SEM, n = 36) vs. control CSF (228 +/- 36, n = 27); p < 0.0001. These data support the hypothesis that transglutaminase activity is increased in HD brain in vivo.
authors.affiliation: Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Jeitner
authors.forename: M B
authors.initials: MB
authors.lastname: Bogdanov
authors.forename: W R
authors.initials: WR
authors.lastname: Matson
authors.forename: Y
authors.initials: Y
authors.lastname: Daikhin
authors.forename: M
authors.initials: M
authors.lastname: Yudkoff
authors.forename: J E
authors.initials: JE
authors.lastname: Folk
authors.forename: L
authors.initials: L
authors.lastname: Steinman
authors.forename: S E
authors.initials: SE
authors.lastname: Browne
authors.forename: M F
authors.initials: MF
authors.lastname: Beal
authors.forename: J P
authors.initials: JP
authors.lastname: Blass
authors.forename: A J
authors.initials: AJ
authors.lastname: Cooper
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D004151:Dipeptides / Q000134:cerebrospinal fluid*; D004563:Electrochemistry; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000134:cerebrospinal fluid*; D008297:Male; D011865:Radioisotope Dilution Technique; D011503:Transglutaminases / Q000378:metabolism; D009764:o-Phthalaldehyde / Q000737:chemistry
chemical_list: D004151:Dipeptides; C001299:epsilon-(gamma-glutamyl)-lysine; D009764:o-Phthalaldehyde; D011503:Transglutaminases