title: 14-3-3 protein is a component of Lewy bodies in Parkinson's disease-mutation analysis and association studies of 14-3-3 eta.
abstract: Mutations in alpha-synuclein have been identified in some rare families with autosomal dominant Parkinson's disease (PD). The synuclein gene family shares physical and functional homology with 14-3-3 proteins and binds to 14-3-3 proteins and to its ligands. We therefore investigated whether 14-3-3 proteins are also involved in the pathogenesis of PD. Here we demonstrate that 14-3-3 proteins are colocalized with Lewy bodies in PD. We investigated the 14-3-3 eta (YWHAH) gene by mutation analysis and association studies as it maps to human chromosome 22q12.1-q13.1, a region which has been recently implicated in PD and carried out immunohistochemical studies of Lewy bodies with two different 14-3-3 eta antibodies. In 358 sporadic and familial PD patients, disease causing mutations were not identified. Furthermore, association studies with intragenic polymorphisms do not provide evidence for an involvement of 14-3-3 eta in the pathogenesis of PD. In accordance with these findings, there was no staining of substantia nigra Lewy bodies with antibodies specific for the 14-3-3 eta subunit.
authors.affiliation: Department of Medical Genetics, Children's Hospital, University Rostock, Rembrandt Str. 16/17, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Ubl
authors.forename: Daniela
authors.initials: D
authors.lastname: Berg
authors.forename: Carsten
authors.initials: C
authors.lastname: Holzmann
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
authors.forename: Klaus
authors.initials: K
authors.lastname: Berger
authors.forename: Thomas
authors.initials: T
authors.lastname: Arzberger
authors.forename: Antje
authors.initials: A
authors.lastname: Bornemann
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
mesh_terms: D048948:14-3-3 Proteins; D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002892:Chromosomes, Human, Pair 22; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; C482984:YWHAH protein, human; D014446:Tyrosine 3-Monooxygenase