Ubl Andreas, Berg Daniela, Holzmann Carsten, Krüger Rejko, Berger Klaus, Arzberger Thomas, Bornemann Antje, Riess Olaf
Department of Medical Genetics, Children's Hospital, University Rostock, Rembrandt Str. 16/17, Germany.
Brain Res Mol Brain Res. 2002 Dec;108(1-2):33-9. doi: 10.1016/s0169-328x(02)00510-7.
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.
在一些患常染色体显性帕金森病（PD）的罕见家族中已发现α-突触核蛋白发生突变。突触核蛋白基因家族与14-3-3蛋白存在物理和功能同源性，并能与14-3-3蛋白及其配体结合。因此，我们研究了14-3-3蛋白是否也参与帕金森病的发病机制。在此我们证明，在帕金森病中14-3-3蛋白与路易小体共定位。我们通过突变分析和关联研究对14-3-3η（YWHAH）基因进行了研究，因为该基因定位于人类染色体22q12.1 - q13.1，该区域最近被认为与帕金森病有关，并且我们用两种不同的14-3-3η抗体对路易小体进行了免疫组化研究。在358例散发性和家族性帕金森病患者中，未发现致病突变。此外，与基因内多态性的关联研究也未提供证据表明14-3-3η参与帕金森病的发病机制。根据这些发现，用针对14-3-3η亚基的特异性抗体对黑质路易小体进行染色时未发现阳性结果。
