Pathogenic mutations in Parkinson disease

被引:182
作者
Tan, Eng-King
Skipper, Lisa M.
机构
[1] Singapore Gen Hosp, Dept Neurol, Singapore 169608, Singapore
[2] Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL USA
关键词
familial; sporadic; gene; mutation; neurodegeneration; Parkinson disease; PD;
D O I
10.1002/humu.20507
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Parkinson disease (PD; Parkinson's) is the second most common neurodegenerative disease, characterized by the progressive loss of dopamine neurons and the accumulation of Lewy bodies. Increasing evidence suggests that deficits in mitochondrial function, oxidative and nitrosative stress, the accumulation of aberrant or misfolded proteins, and ubiquitin-proteasome system (UPS) dysfunction may represent the principal molecular pathways that commonly underlie the pathogenesis. The relative role of genetic and environmental factors has been the focus of research and debate. The recent discovery of a number of disease causing genes (SNCA, Parkin/PARK2, UCHL1, PINK1, DJ1/PARK7, and LRRK2) in familial and sporadic forms of PD has provided considerable insights into the pathophysiology of this complex disorder. The frequency of these gene mutations may vary according to ethnicity and to the specific gene. A gene dosage effect is observed in some cases, and the phenotype of some of the mutation carriers closely resembles typical PD. Penetrance of some of the recurrent mutations is incomplete and may vary with age. Further research to unravel the etiopathology could identify biochemical or genetic markers for potential neuroprotective trials.
引用
收藏
页码:641 / 653
页数:13
相关论文
共 175 条
[1]   Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system [J].
Abeliovich, A ;
Schmitz, Y ;
Fariñas, I ;
Choi-Lundberg, D ;
Ho, WH ;
Castillo, PE ;
Shinsky, N ;
Verdugo, JMG ;
Armanini, M ;
Ryan, A ;
Hynes, M ;
Phillips, H ;
Sulzer, D ;
Rosenthal, A .
NEURON, 2000, 25 (01) :239-252
[2]   A heterozygous effect for PINK1 mutations in Parkinson's disease? [J].
Abou-Sleiman, Patrick M. ;
Muqit, Miratul M. K. ;
McDonald, Neil Q. ;
Yang, Yan Xiang ;
Gandhi, Sonia ;
Healy, Daniel G. ;
Harvey, Kirsten ;
Harvey, Robert J. ;
Deas, Emma ;
Hatia, Kailash ;
Quinn, Niall ;
Lees, Andrew ;
Latchman, David S. ;
Wood, Nicholas W. .
ANNALS OF NEUROLOGY, 2006, 60 (04) :414-419
[3]   The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease [J].
Bandopadhyay, R ;
Kingsbury, AE ;
Cookson, MR ;
Reid, AR ;
Evans, IM ;
Hope, AD ;
Pittman, AM ;
Lashley, T ;
Canet-Aviles, R ;
Miller, DW ;
McLendon, C ;
Strand, C ;
Leonard, AJ ;
Abou-Sleiman, PM ;
Healy, DG ;
Ariga, H ;
Wood, NW ;
de Silva, R ;
Revesz, T ;
Hardy, JA ;
Lees, AJ .
BRAIN, 2004, 127 :420-430
[4]   Alpha-synuclein and Parkinson's disease:: Implications from the screening of more than 1,900 patients [J].
Berg, D ;
Niwar, M ;
Maass, S ;
Zimprich, A ;
Möller, JC ;
Wuellner, U ;
Schmitz-Hübsch, T ;
Klein, C ;
Tan, EK ;
Schöls, L ;
Marsh, L ;
Dawson, TM ;
Janetzky, B ;
Müller, T ;
Woitalla, D ;
Kostic, V ;
Pramstaller, PP ;
Oertel, WH ;
Bauer, P ;
Krueger, R ;
Gasser, T ;
Riess, O .
MOVEMENT DISORDERS, 2005, 20 (09) :1191-1194
[5]  
Bonifati V, 2005, Minerva Med, V96, P175
[6]   Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism [J].
Bonifati, V ;
Rizzu, P ;
van Baren, MJ ;
Schaap, O ;
Breedveld, GJ ;
Krieger, E ;
Dekker, MCJ ;
Squitieri, F ;
Ibanez, P ;
Joosse, M ;
van Dongen, JW ;
Vanacore, N ;
van Swieten, JC ;
Brice, A ;
Meco, G ;
van Duijn, CM ;
Oostra, BA ;
Heutink, P .
SCIENCE, 2003, 299 (5604) :256-259
[7]   Pesticides and Parkinson's disease - Is there a link? [J].
Brown, TP ;
Rumsby, PC ;
Capleton, AC ;
Rushton, L ;
Levy, LS .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2006, 114 (02) :156-164
[8]  
Cabin DE, 2002, J NEUROSCI, V22, P8797
[9]   The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization [J].
Canet-Avilés, RM ;
Wilson, MA ;
Miller, DW ;
Ahmad, R ;
McLendon, C ;
Bandyopadhyay, S ;
Baptista, MJ ;
Ringe, D ;
Petsko, GA ;
Cookson, MR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (24) :9103-9108
[10]   α-synuclein locus duplication as a cause of familial Parkinson's disease [J].
Chartier-Harlin, MC ;
Kachergus, J ;
Roumier, C ;
Mouroux, V ;
Douay, X ;
Lincoln, S ;
Levecque, C ;
Larvor, L ;
Andrieux, J ;
Hulihan, M ;
Waucquier, N ;
Defebvre, L ;
Amouyel, P ;
Farrer, M ;
Destée, A .
LANCET, 2004, 364 (9440) :1167-1169