The role of glucocerebrosidase mutations in parkinson disease and lewy body disorders

Current Neurology and Neuroscience Reports

Volumn 10, Issue 3, 2010, Pages 190-198

  Velayati, Arash ^a   Yu, W Haung ^b   Sidransky, Ellen ^a  

^a NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^b Och Spine at New York Presbyterian Hospitals   (United States)

Author keywords

Alpha synuclein; Gaucher disease; Glucoceerebrosidase; Lew body disorders; Parkinson disease

Indexed keywords

ALPHA SYNUCLEIN; GLUCOSYLCERAMIDASE; PROTEASOME; UBIQUITIN;

AUTOPHAGY; DIFFUSE LEWY BODY DISEASE; ENDOPLASMIC RETICULUM STRESS; GAUCHER DISEASE; GENE FREQUENCY; GENE MUTATION; GENE SEQUENCE; GENETIC ANALYSIS; GENETIC POLYMORPHISM; GENETIC SCREENING; HETEROZYGOSITY; HETEROZYGOTE; HISTOPATHOLOGY; HUMAN; PARKINSON DISEASE; PARKINSONISM; PATHOPHYSIOLOGY; PHENOTYPE; REVIEW; RISK FACTOR; ANIMAL; ENZYMOLOGY; GENETIC PREDISPOSITION; GENETICS; MUTATION; PHYSIOLOGY;

ANIMALS; GENETIC PREDISPOSITION TO DISEASE; GLUCOSYLCERAMIDASE; HUMANS; LEWY BODY DISEASE; MUTATION; PARKINSON DISEASE;

EID: 77954933661     PISSN: 15284042     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11910-010-0102-x     Document Type: Review

References (80)

1. Beutler E: Gaucher disease: new molecular approaches to diagnosis and treatment. Science 1992, 256:794-799.
2. Horowitz M, Wilder S, Horowitz Z, et al.: The human glucocerebrosidase gene and pseudogene: structure and evolution. Genomics 1989, 4:87-96.
3. Sorge J, West C, Westwood B, Beutler E: Molecular cloning and nucleotide sequence of human glucocerebrosidase cDNA. Proc Nat Acad Sci U S A 1985, 82:7289-7293.
4. Barneveld RA, Keijzer W, Tegelaers FP, et al.: Assignment of the gene coding for human beta-glucocerebrosidase to the region q21-q31 of chromosome 1 using monoclonal antibodies. Hum Genet 1993, 64:227-231.
5. Winfield SL, Tayebi N, Martin BM, et al.: Identification of three additional genes contiguous to the glucocerebrosidase locus on chromosome 1q21: implications for Gaucher disease. Genome Res 1997, 7:1020-1026.
6. Sorge J, Gross E, West C, Beutler E: High level transcription of the glucocerebrosidase pseudogene in normal subjects and patients with Gaucher disease. J Clin Invest 1990, 86:1137-1141.
7. Gaucher PCE: On primary epithelioma of the spleen: idiopathic hypertrophy of the spleen without leukemia. Thesis, Doctor of Medicine. Paris: Octave Doin; 1882.
8. • Hruska KS, LaMarca ME, Scott CR, Sidransky E: Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA). Hum Mutat 2008, 29:567-583. This work provides a comprehensive review of the structure of GBA and the mutations identified.
9. Koprivica V, Stone DL, Park JK, et al.: Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Am J Hum Genet 2000, 66:1777-1786.
10. Goker-Alpan O, Hruska KS, Orvisky E, et al.: Divergent phenotypes in Gaucher disease implicate the role of modifiers. J Med Genet 2005, 42:e37.
11. Neudorfer O, Giladi N, Elstein D, et al.: Occurrence of Parkinson's syndrome in type I Gaucher disease. QJM 1996, 89:691-694.
12. Machaczka M, Rucinska M, Skotnicki AB, Jurczak W: Parkinson's syndrome preceding clinical manifestation of Gaucher's disease. Am J Hematol 1999, 61:216-217.
13. Várkonyi J, Rosenbaum H, Baumann N, et al.: Gaucher disease associated with parkinsonism: four further case reports. Am J Med Genet A 2003, 116A:348-351.
14. Goker-Alpan O, Schiffmann R, LaMarca ME, et al.: Parkinsonism among Gaucher disease carriers. J Med Genet 2004, 41:937-940.
15. Halperin A, Elstein D, Zimran A: Increased incidence of Parkinson disease among relatives of patients with Gaucher disease. Blood Cells Mol Dis 2006, 36:426-428.
16. Goker-Alpan O, Giasson BI, Eblan MJ, et al.: Glucocerebrosidase mutations are an important risk factor for Lewy body disorders. Neurology 2006, 67:908-910.
17. Tayebi N, Callahan M, Madike V, et al.: Gaucher disease and parkinsonism: a phenotypic and genotypic characterization. Mol Genet Metab 2001, 73:313-321.
18. Tayebi N, Walker J, Stubblefield B, et al.: Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism? Mol Genet Metab 2003, 79:104-109.
19. Lwin A, Orvisky E, Goker-Alpan O, et al.: Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab 2004, 81(1):70-73.
20. Park JK, Tayebi N, Stubblefield BK, et al.: The E326K mutation and Gaucher disease: mutation or polymorphism? Clin Genet 2002, 61(1):32-34.
21. Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R: Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med 2004, 351(19):1972-1977.
22. Sato C, Morgan A, Lang AE, et al.: Analysis of the glucocerebrosidase gene in Parkinson's disease. Mov Disord 2005, 20 (3):367-370.
23. Toft M, Pielsticker L, Ross OA, et al.: Glucocerebrosidase gene mutations and Parkinson disease in the Norwegian population. Neurology 2006, 66(3):415-417.
24. Eblan MJ, Nguyen J, Ziegler SG, et al.: Glucocerebrosidase mutations are also found in subjects with early-onset parkinsonism from Venezuela. Mov Disord 2006, 21(2):282-283.
25. Tan EK, Tong J, Fook-Chong S, et al.: Glucocerebrosidase mutations and risk of Parkinson disease in Chinese patients. Arch Neurol 2007, 64(7):1056-1058.
26. Ziegler SG, Eblan MJ, Gutti U, et al.: Glucocerebrosidase mutations in Chinese subjects from Taiwan with sporadic Parkinson disease. Mol Genet Metab 2007, 91(2):195-200.
27. Clark LN, Ross BM, Wang Y, et al.: Mutations in the glucocerebrosidase gene are associated with early-onset Parkinson disease. Neurology 2007, 69(12):1270-1277.
28. Wu YR, Chen CM, Chao CY, et al.: Glucocerebrosidase gene mutation is a risk factor for early onset of Parkinson disease among Taiwanese. J Neurol Neurosurg Psychiatry 2007, 78 (9):977-979.
29. • Gan-Or Z, Giladi N, Rozovski U, et al.: Genotype-phenotype correlations between GBA mutations and Parkinson disease risk and onset. Neurology 2008, 70(24):2277-2283. This study included the largest cohort of Ashkenazi Jewish subjects with parkinsonism screened for GBA mutations.
30. Spitz M, Rozenberg R, Pereira Lda V, Reis Barbosa E: Association between Parkinson's disease and glucocerebrosidase mutations in Brazil. Parkinsonism Relat Disord 2008, 14(1):58-62.
31. • Neumann J, Bras J, Deas E, et al.: Glucocerebrosidase mutations in clinical and pathologically proven Parkinson's disease. Brain 2009, 132(Pt 7):1783-1794. The authors sequenced the GBA gene in a large series of brains from subjects with PD as well as controls. They identified mutations in 4.2% of patients versus 1.2% of controls.
32. Nichols WC, Pankratz N, Marek DK, et al.; Parkinson Study Group-PROGENI Investigators: Mutations in GBA are associated with familial Parkinson disease susceptibility and age at onset. Neurology 2009, 72(4):310-316.
33. Kalinderi K, Bostantjopoulou S, Paisan-Ruiz C, et al.: Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Greece. Neurosci Lett 2009, 452(2):87-89.
34. • Mitsui J, Mizuta I, Toyoda A, et al.: Mutations for Gaucher disease confer high susceptibility to Parkinson disease. Arch Neurol 2009, 66(5):571-576. This study, conducted in Japan, demonstrates that in this cohort, GBA mutations are encountered frequently in subjects with PD. The spectrum of mutations, however, differed from cohorts of other ethnicities.
35. Bras J, Paisan-Ruiz C, Guerreiro R, et al.: Complete screening for glucocerebrosidase mutations in Parkinson disease patients from Portugal. Neurobiol Aging 2009, 30(9):1515-1517.
36. •• Sidransky E, Nalls MA, Aasly JO, et al.: Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med 2009, 361:1651-1661. This multicenter international collaborative study combined the results from 16 different centers in four continents. Studying more than 5000 patients and an equal number of controls, the authors demonstrated that the odds ratio for carrying a GBA mutation in patients with PD was greater than 5.
37. Gutti U, Fung HC, Hruska KS, et al.: The need for appropriate genotyping strategies for glucocerebrosidase mutations in cohorts with Parkinson disease. Arch Neurol 2008, 65:850-851.
38. Wan L, Hsu CM, Tsai CH, et al.: Mutation analysis of Gaucher disease patients in Taiwan: high prevalence of the RecNciI and L444P mutations. Blood Cells Mol Dis 2006, 36:422-425.
39. McKeith IG, Dickson DW, Lowe J, et al.: Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 2005, 65:1863-1872.
40. Wenning GK, Jellinger KA: The role of alpha-synuclein in the pathogenesis of multiple system atrophy. Acta Neuropathol 2005, 109:129-140.
41. Mata IF, Samii A, Schneer SH, et al.: Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders. Arch Neurol 2008, 65:379-382.
42. Farrer MJ, Williams LN, Algom AA, et al.: Glucosidase-beta variations and Lewy body disorders. Parkinsonism Relat Disord 2009, 15:414-416.
43. Clark LN, Kartsaklis LA, Wolf Gilbert R, et al.: Association of glucocerebrosidase mutations with dementia with lewy bodies. Arch Neurol 2009, 66:578-583.
44. Segarane B, Li A, Paudel R, et al.: Glucocerebrosidase mutations in 108 neuropathologically confirmed cases of multiple system atrophy. Neurology 2009, 72:1185-1186.
45. Jamrozik Z, Lugowska A, Slawek J, Kwiecinski H: Glucocerebrosidase mutations p.L444P and p.N370S are not associated with multisystem atrophy, progressive supranuclear palsy and corticobasal degeneration in Polish patients. J Neurol 2009 Nov 1 (Epub ahead of print).
46. Bembi B, Zambito Marsala S, Sidransky E, et al.: Gaucher's disease with Parkinson's disease: clinical and pathological aspects. Neurology 2003, 61:99-101.
47. Wong K, Sidransky E, Verma A, et al.: Neuropathology provides clues to the pathophysiology of Gaucher disease. Mol Genet Metab 2004, 82:192-207.
48. Kono S, Shirakawa K, Ouchi Y, et al.: Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier. J Neurol Sci 2007, 252:181-184.
49. Goker-Alpan O, Lopez G, Vithayathil J, et al.: The spectrum of parkinsonian manifestations associated with glucocerebrosidase mutations. Arch Neurol 2008, 65:1353-1357.
50. Gan-Or Z, Giladi N, Orr-Urtreger A: Differential phenotype in Parkinson's disease patients with severe versus mild GBA mutations. Brain 2009, 132:e125.
51. Hardy J, Lewis P, Revesz T, et al.: The genetics of Parkinson's syndromes: a critical review. Curr Opin Genet Dev 2009, 19:254-265.
52. Bras J, Singleton A, Cookson MR, Hardy J: Emerging pathways in genetic Parkinson's disease: potential role of ceramide metabolism in Lewy body disease. FEBS J 2008, 275:5767-5773.
53. Conradi NG, Sourander P, Nilsson O, et al.: Neuropathology of the Norrbottnian type of Gaucher disease. Morphological and biochemical studies. Acta Neuropathol 1984, 65:99-109.
54. Jo E, McLaurin J, Yip CM, et al.: alpha-Synuclein membrane interactions and lipid specificity. J Biol Chem 2000, 275:34328-34334.
55. Schlossmacher MG, Cullen V, Müthing J: The glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med 2005, 352:728-731.
56. Simons K, Gruenberg J: Jamming the endosomal system: lipid rafts and lysosomal storage diseases. Trends Cell Biol 2000, 10:459-462.
57. Martinez Z, Zhu M, Han S, Fink AL: GM1 specifically interacts with alpha-synuclein and inhibits fibrillation. Biochemistry 2007, 46:1868-1877.
58. Sharon R, Bar-Joseph I, Frosch MP, et al.: The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson's disease. Neuron 2003, 37:583-595.
59. Manning-Bog AB, Schüle B, Langston JW: Alpha- synucleinglucocerebrosidase interactions in pharmacological Gaucher models: a biological link between Gaucher disease and parkinsonism. Neurotoxicology 2009, 30(6):1127-1132.
60. Sawkar AR, Adamski-Werner SL, Cheng WC, et al.: Gaucher disease-associated glucocerebrosidases show mutation-dependent chemical chaperoning profiles. Chem Biol 2005, 12:1235-1244.
61. de Duve C: From cytases to lysosomes. Fed Proc 1964, 23:1045-1049.
62. Essner E, Novikoff AB: Localization of acid phosphatase activity in hepatic lysosomes by means of electron microscopy. J Biophys Biochem Cytol 1961, 9:773-784.
63. Ramirez A, Heimbach A, Grundemann J, et al.: Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 2006, 38:1184-1191.
64. Di Fonzo A, Chien HF, Socal M, et al.: ATP13A2 missense mutations in juvenile parkinsonism and young onset Parkinson disease. Neurology 2007, 68:1557-1562.
65. Cuervo AM, Stefanis L, Fredenburg R, et al.: Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 2004, 305:1292-1295.
66. Martinez-Vicente M, Talloczy Z, Kaushik S, et al.: Dopaminemodified alpha-synuclein blocks chaperone-mediated autophagy. J Clin Invest 2008, 118:777-788.
67. Klionsky DJ, Emr SD: Autophagy as a regulated pathway of cellular degradation. Science 2000, 290:1717-1721.
68. Sou YS, Tanida I, Komatsu M, et al.: Phosphatidylserine in addition to phosphatidylethanolamine is an in vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16. J Biol Chem 2006, 281:3017-3024.
69. Webb JL, Ravikumar B, Atkins J, et al.: Alpha-Synuclein is degraded by both autophagy and the proteasome. J Biol Chem 2003, 278:25009-25013.
70. Yu WH, Dorado B, Figueroa HY, et al.: Metabolic activity determines efficacy of macroautophagic clearance of pathological oligomeric alpha-synuclein. Am J Pathol 2009, 175:736-747.
71. Spencer B, Potkar R, Trejo M, et al.: Beclin 1 gene transfer activates autophagy and ameliorates the neurodegenerative pathology in alpha-synuclein models of Parkinson's and Lewy body diseases. J Neurosci 2009, 29:13578-13588.
72. Hara T, Nakamura K, Matsui M, et al.: Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006, 441:885-889.
73. Komatsu M, Waguri S, Chiba T, et al.: Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006, 441:880-884.
74. Singh R, Kaushik S, Wang Y, et al.: Autophagy regulates lipid metabolism. Nature 2009, 458:1131-1135.
75. Scarlatti F, Bauvy C, Ventruti A, et al.: Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1. J Biol Chem 2004, 279:18384-18391.
76. Dawson TM: Parkin and defective ubiquitination in Parkinson's disease. J Neural Transm Suppl 2006, 70:209-213.
77. Ron I, Horowitz M: ER retention and degradation as the molecular basis underlying Gaucher disease heterogeneity. Hum Mol Genet 2005, 14:2387-2398.
78. Horowitz M, Ron I: Interaction between parkin and glucocerebrosidase: a possible link between Parkinson disease and Gaucher disease. Mol Genet Metab 2009, 96:S27.
79. Clark LN, Nicolai A, Afridi S, et al.: Pilot association study of the beta-glucocerebrosidase N370S allele and Parkinson's disease in subjects of Jewish ethnicity. Mov Disord 2005, 20:100-103.
80. De Marco EV, Annesi G, Tarantino P, et al.: Glucocerebrosidase gene mutations are associated with Parkinson's disease in southern Italy. Mov Disord 2008, 23:460-463.