Parkin and synphilin-1 isoform expression changes in Lewy body diseases

被引:34
作者
Humbert, Jordi
Beyer, Katrin [1 ]
Carrato, Cristina
Mate, Jose L.
Ferrer, Isidro
Ariza, Aurelio
机构
[1] Univ Autonoma Barcelona, Hosp Germans Trias & Pujol, Dept Pathol, Badalona 08916, Spain
[2] Hosp Bellvitge Princeps Espanya, Inst Neuropathol, Lhospitalet De Llobregat, Spain
关键词
dementia with lewy bodies; Parkinson disease; lewy body variant of Alzheimer disease; differential isoform expression; transcript variant;
D O I
10.1016/j.nbd.2007.03.007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Alternative splicing gives rise to at least seven parkin and eight synphilin-1 isoforms. Since both parkin and synphifn-1 have been involved in Lewy body (LB) formation, we decided to explore whether their isoforms are differentially expressed in LB diseases. With this aim, we studied relative mRNA expression levels of parkin and synphilin-1 isoforms in the frontal cortices of patients with dementia with LBs, the LB variant of Alzheimer's disease and Parkinson's disease and compared the findings with those obtained from Alzheimer's disease patients and control individuals. Duplex real-time PCR reactions, with beta-actin as internal standard, were carried out in a LightCycler. mRNA expression levels of parkin and synphilin-1 isoforms were seen to be specifically altered in each of the LB diseases studied. These findings suggest that parkin and synphilin-1 isoform expression changes play a significant role in the pathogenesis of LB diseases. (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:681 / 687
页数:7
相关论文
共 28 条
[1]   Upregulation of amyloid precursor protein isoforms containing Kunitz protease inhibitor in dementia with Lewy bodies [J].
Beyer, K ;
Lao, JI ;
Carrato, C ;
Mate, JL ;
López, D ;
Ferrer, I ;
Ariza, A .
MOLECULAR BRAIN RESEARCH, 2004, 131 (1-2) :131-135
[2]   Differential expression of α-synuclein isoforms in dementia with Lewy bodies [J].
Beyer, K ;
Lao, JI ;
Carrato, C ;
Mate, JL ;
López, D ;
Ferrer, I ;
Ariza, A .
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2004, 30 (06) :601-607
[3]   Low alpha-synuclein 126 mRNA levels in dementia with Lewy bodies and Alzheimer disease [J].
Beyer, Katrin ;
Humbert, Jordi ;
Ferrer, Anna ;
Lao, Jose I. ;
Carrato, Cristina ;
Lopez, Dolores ;
Ferrer, Isidro ;
Ariza, Aurelio .
NEUROREPORT, 2006, 17 (12) :1327-1330
[4]   Co-association of parkin and α-synuclein [J].
Choi, P ;
Golts, N ;
Snyder, H ;
Chong, M ;
Petrucelli, L ;
Hardy, J ;
Sparkman, D ;
Cochran, E ;
Lee, JM ;
Wolozin, B .
NEUROREPORT, 2001, 12 (13) :2839-2843
[5]   Parkin ubiquitinates the α-synuclein-interacting protein, synphilin-1:: implications for Lewy-body formation in Parkinson disease [J].
Chung, KKK ;
Zhang, Y ;
Lim, KL ;
Tanaka, Y ;
Huang, H ;
Gao, J ;
Ross, CA ;
Dawson, VL ;
Dawson, TM .
NATURE MEDICINE, 2001, 7 (10) :1144-1150
[6]   The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration [J].
Corti, O ;
Hampe, C ;
Koutnikova, H ;
Darios, F ;
Jacquier, S ;
Prigent, A ;
Robinson, JC ;
Pradier, L ;
Ruberg, M ;
Mirande, M ;
Hirsch, E ;
Rooney, T ;
Fournier, A ;
Brice, A .
HUMAN MOLECULAR GENETICS, 2003, 12 (12) :1427-1437
[7]   Parkin transcript variants in rat and human brain [J].
D'Agata, V ;
Cavallaro, S .
NEUROCHEMICAL RESEARCH, 2004, 29 (09) :1715-1724
[8]   Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions [J].
Engelender, S ;
Kaminsky, Z ;
Guo, X ;
Sharp, AH ;
Amaravi, RK ;
Kleiderlein, JJ ;
Margolis, RL ;
Troncoso, JC ;
Lanahan, AA ;
Worley, PF ;
Dawson, VL ;
Dawson, TM ;
Ross, CA .
NATURE GENETICS, 1999, 22 (01) :110-114
[9]   Synphilin-1A:: An aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from α-synucleinopathy patients [J].
Eyal, A ;
Szargel, R ;
Avraham, E ;
Liani, E ;
Haskin, J ;
Rott, R ;
Engelender, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (15) :5917-5922
[10]   Neuropathology of Parkinson's disease [J].
Forno, LS .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 1996, 55 (03) :259-272