Glucocerebrosidase mutations and the pathogenesis of Parkinson disease

被引:81
作者
Beavan, Michelle S. [1 ]
Schapira, Anthony H. V. [1 ]
机构
[1] UCL, Inst Neurol, Dept Clin Neurosci, London NW3 2PF, England
基金
英国惠康基金;
关键词
Gaucher disease; glucocerebrosidase; Parkinson disease; CHAPERONE-MEDIATED AUTOPHAGY; GAUCHER-DISEASE; ALPHA-SYNUCLEIN; GENE-MUTATIONS; EARLY-ONSET; RISK-FACTOR; PROTEASOMAL FUNCTION; HIGH SUSCEPTIBILITY; BETA-GLUCOSIDASE; L444P MUTATION;
D O I
10.3109/07853890.2013.849003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Parkinson disease (PD) is the second most common neurodegenerative disease after Alzheimer disease with a lifetime risk in the UK population of almost 5%. An association between PD and Gaucher disease (GD) derived from the observation that GD patients and their heterozygous carrier relatives were at increased risk of PD. GD is an autosomal recessive lysosomal storage disorder caused by homozygous mutations in the gene encoding glucocerebrosidase (GBA). Approximately 5%-10% of PD patients have GBA mutations, making these mutations numerically the most important genetic predisposing risk factor for the development of PD identified to date. GBA mutations result in a phenotype that is virtually indistinguishable clinically, pharmacologically, and pathologically from sporadic PD, except GBA mutations result in a slightly earlier age of onset and more frequent cognitive impairment among PD patients. The mechanisms by which GBA mutations result in PD are not yet understood. Both reduced glucocerebrosidase enzyme (GCase) activity with lysosomal dysfunction, and unfolded protein response (UPR) with endoplasmic reticulum-associated degradation (ERAD) and stress are considered contributory.
引用
收藏
页码:511 / 521
页数:11
相关论文
共 132 条
[1]   Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews [J].
Aharon-Peretz, J ;
Rosenbaum, H ;
Gershoni-Baruch, R .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (19) :1972-1977
[2]   Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study [J].
Alcalay, R. N. ;
Caccappolo, E. ;
Mejia-Santana, H. ;
Tang, M. -X. ;
Rosado, L. ;
Reilly, M. Orbe ;
Ruiz, D. ;
Ross, B. ;
Verbitsky, M. ;
Kisselev, S. ;
Louis, E. ;
Comella, C. ;
Colcher, A. ;
Jennings, D. ;
Nance, M. ;
Bressman, S. ;
Scott, W. K. ;
Tanner, C. ;
Mickel, S. ;
Andrews, H. ;
Waters, C. ;
Fahn, S. ;
Cote, L. ;
Frucht, S. ;
Ford, B. ;
Rezak, M. ;
Novak, K. ;
Friedman, J. H. ;
Pfeiffer, R. ;
Marsh, L. ;
Hiner, B. ;
Siderowf, A. ;
Payami, H. ;
Molho, E. ;
Factor, S. ;
Ottman, R. ;
Clark, L. N. ;
Marder, K. .
NEUROLOGY, 2012, 78 (18) :1434-1440
[3]   Chaperone-Mediated Autophagy Markers in Parkinson Disease Brains [J].
Alvarez-Erviti, Lydia ;
Rodriguez-Oroz, Maria C. ;
Cooper, J. Mark ;
Caballero, Cristina ;
Ferrer, Isidro ;
Obeso, Jose A. ;
Schapira, Anthony H. V. .
ARCHIVES OF NEUROLOGY, 2010, 67 (12) :1464-1472
[4]   Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers [J].
Anheim, M. ;
Elbaz, A. ;
Lesage, S. ;
Durr, A. ;
Condroyer, C. ;
Viallet, F. ;
Pollak, P. ;
Bonaiti, B. ;
Bonaiti-Pellie, C. ;
Brice, A. .
NEUROLOGY, 2012, 78 (06) :417-420
[5]  
[Anonymous], 1882, THESIS
[6]   The proteasomal inhibition model of Parkinson's disease: "Boon or bust"? [J].
Beal, Flint ;
Lang, Anthony .
ANNALS OF NEUROLOGY, 2006, 60 (02) :158-161
[7]   Gaucher's disease with Parkinson's disease - Clinical and pathological aspects [J].
Bembi, B ;
Marsala, SZ ;
Sidransky, E ;
Ciana, G ;
Carrozzi, M ;
Zorzon, M ;
Martini, C ;
Gioulis, M ;
Pittis, MG ;
Capus, L .
NEUROLOGY, 2003, 61 (01) :99-101
[8]   Phenotype in patients with Gaucher disease and Parkinson disease [J].
Ben Chetrit, Eli ;
Alcalay, Roy N. ;
Steiner-Birmanns, Bettina ;
Altarescu, Gheona ;
Phillips, Mici ;
Elstein, Deborah ;
Zimran, Ari .
BLOOD CELLS MOLECULES AND DISEASES, 2013, 50 (03) :218-221
[9]   Ambroxol as a pharmacological chaperone for mutant glucocerebrosidase [J].
Bendikov-Bar, Inna ;
Maor, Gali ;
Filocamo, Mirella ;
Horowitz, Mia .
BLOOD CELLS MOLECULES AND DISEASES, 2013, 50 (02) :141-145
[10]   Transcranial sonography in movement disorders [J].
Berg, Daniela ;
Godau, Jana ;
Walter, Uwe .
LANCET NEUROLOGY, 2008, 7 (11) :1044-1055