The genetics of Parkinson's disease

Current Opinion in Genetics and Development

Volumn 10, Issue 3, 2000, Pages 292-298

  Rohan De Silva, Ha ^a,b   Khan, Naheed L ^b   Wood, Nicholas W ^b  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA SYNUCLEIN; HYDROLASE; UBIQUITIN;

CHROMOSOME 22; ENVIRONMENTAL FACTOR; GENE LOCUS; GENE MAPPING; GENE MUTATION; GENETIC HETEROGENEITY; HUMAN; MOLECULAR GENETICS; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW;

PARKINSONIA;

EID: 0008209418     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(00)00082-4     Document Type: Review

References (45)

1. de Rijk M.C., Tzourio C., Breteler M.M., Dartigues J.F., Amaducci L., Lopez-Pousa S., Manubens-Bertran J.M., Alperovitch A., Rocca W.A. Prevalence of parkinsonism and Parkinson's disease in Europe: the EUROPARKINSON Collaborative Study. European community concerted action on the epidemiology of Parkinson's disease. J Neurol Neurosurg Psychiatry. 62:1997;10-15.
2. Gowers, W.R.A Manual of Diseases of the Nervous System. Philadelphia, PA: Blakiston; 1893:6366-6657.
3. Elbaz A., Grigoletto F., Baldereschi M., Breteler M.M., Manubens-Bertran J.M., Lopez-Pousa S., Dartigues J.F., Alperovitch A., Tzourio C., Rocca W.A. Familial aggregation of Parkinson's disease: a population-based case-control study in Europe. EUROPARKINSON Study Group. Neurology. 52:1999;1876-1882.
4. 18F]-dopa uptake by positron emission tomography as a measure of striatal dopaminergic dysfunction in subclinical PD. Concordance rates were shown to be highly elevated in MZ twins, and much lower in DZ twins providing compelling evidence of the importance of genetic background in the etiology of sporadic PD.
5. Polymeropoulos M.H., Lavedan C., Leroy E., Ide S.E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R.et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 276:1997;2045-2047.
6. Athanassiadou A., Voutsinas G., Psiouri L., Leroy E., Polymeropoulos M.H., Ilias A., Maniatis G.M., Papapetropoulos T. Genetic analysis of families with Parkinson disease that carry the Ala53Thr mutation in the gene encoding alpha-synuclein. Am J Hum Genet. 65:1999;555-558.
7. Kruger R., Kuhn W., Muller T., Woitalla D., Graeber M., Kosel S., Przuntek H., Epplen J.T., Schols L., Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet. 18:1998;106-108. The identification of a second mutation in a small German kindred confirmed the role of αSYN mutations in PD.
8. Vaughan J.R., Farrer M.J., Wszolek Z.K., Gasser T., Durr A., Agid Y., Bonifati V., DeMichele G., Volpe G., Lincoln S.et al. Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD). Hum Mol Genet. 7:1998;751-753.
9. Scott W.K., Yamaoka L.H., Stajich J.M., Scott B.L., Vance J.M., Roses A.D., Pericak-Vance M.A., Watts R.L., Nance M., Hubble J.et al. The alpha-synuclein gene is not a major risk factor in familial Parkinson disease. Neurogenetics. 2:1999;191-192.
10. Clayton D.F., George J.M. Synucleins in synaptic plasticity and neurodegenerative disorders. J Neurosci Res. 58:1999;120-129. A comprehensive review and update of synuclein function and interactions that proposes a hypothesis of the involvement of synuclein in the turnover of pre-synaptic membranes and synaptic signalling, processes important in learning and memory.
11. Tran P.B., Miller R.J. Aggregates in neurodegenerative disease: crowds and power? Trends Neurol Sci. 22:1999;194-197.
12. Narhi L., Wood S.J., Steavenson S., Jiang Y., Wu G.M., Anafi D., Kaufman S.A., Martin F., Sitney K., Denis P.et al. Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation. J Biol Chem. 274:1999;9843-9846.
13. Conway K.A., Lee S.J., Rochet J.C., Ding T.T., Williamson R.E., Lansbury P.T. Jr. Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's, disease: implications for pathogenesis and therapy. Proc Natl Acad Sci USA. 97:2000;571-576. Accelerated αSYN fibrillisation due to PD mutations is touted as a central mechanism in PD pathogenesis. In this work, the lack of correlation of rates of fibril formation with consumption of αSYN monomers suggested that protofibrillar oligomeric intermediates were the critical neurotoxic species.
14. Leroy E., Boyer R., Auburger G., Leube B., Ulm G., Mezey E., Harta G., Brownstein M.J., Jonnalagada S., Chernova T.et al. The ubiquitin pathway in Parkinson's disease. Nature. 395:1998;451-452.
15. Weinreb P.H., Zhen W., Poon A.W., Conway K.A., Lansbury P.T. Jr. NACP, a protein implicated in Alzheimer's, disease and learning, is natively unfolded. Biochemistry. 35:1996;13709-13715.
16. Davidson W.S., Jonas A., Clayton D.F., George J.M. Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem. 273:1998;9443-9449.
17. Jenco J.M., Rawlingson A., Daniels B., Morris A.J. Regulation of phospholipase D2: selective inhibition of mammalian phospholipase D isoenzymes by alpha- and beta-synucleins. Biochemistry. 37:1998;4901-4909.
18. Ostrerova N., Petrucelli L., Farrer M., Mehta N., Choi P., Hardy J., Wolozin B. Alpha-synuclein shares physical and functional homology with 14-3-3 proteins. J Neurosci. 19:1999;5782-5791. Homology of αSYN to the 14-3-3 proteins and interaction studies support a role of αSYN as a chaperone protein, with the amino-terminal homology domain mediating interaction with 14-3-3 as well as protein kinase C (PKC), BAD and extracellular-regulated kinase (ERK), with inhibition of PKC. These findings give important clues to interactions and pathways that could be involved in neurodegeneration.
19. Siddhanta A., Shields D. Secretory vesicle budding from the trans-gogi network is mediated by phosphatidic acid levels. J Biol Chem. 273:1998;17995-17998.
20. Okochi M., Walter J., Koyama A., Nakajo S., Baba M., Iwatsubo T., Meijer L., Kahle P.J., Haass C. Constitutive phosphorylation of the Parkinson's disease associated alpha-synuclein. J Biol Chem. 275:2000;390-397.
21. Lincoln S., Vaughan J., Wood N., Baker M., Adamson J., Gwinn-Hardy K., Lynch T., Hardy J., Farrer M. Low frequency of pathogenic mutations in the ubiquitin carboxy-terminal hydrolase gene in familial Parkinson's disease. Neuroreport. 10:1999;427-429.
22. Farrer M., Gwinn-Hardy K., Muenter M., DeVrieze F.W., Crook R., Perez-Tur J., Lincoln S., Maraganore D., Adler C., Newman S.et al. A chromosome 4p haplotype segregating with Parkinson's disease and postural tremor. Hum Mol Genet. 8:1999;81-85.
23. Gasser T., Muller-Myhsok B., Wszolek Z.K., Oehlmann R., Calne D.B., Bonifati V., Bereznai B., Fabrizio E., Vieregge P., Horstmann R.D. A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nat Genet. 18:1998;262-265.
24. Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 392:1998;605-608. This paper first reports the discovery of the parkin gene and homologous deletions that are the cause of autosomal-dominant juvenile parkinsonism in Japanese families.
25. Hattori N., Matsumine H., Asakawa S., Kitada T., Yoshino H., Elibol B., Brookes A.J., Yamamura Y., Kobayashi T., Wang M.et al. Point mutations (Thr240Arg and Gln311Stop) [correction of Thr240Arg and Ala311Stop] in the parkin gene. Biochem Biophys Res Commun. 249:1998;754-758.
26. Lucking C.B., Abbas N., Durr A., Bonifati V., Bonnet A.M., de Broucker T., De Michele G., Wood N.W., Agid Y., Brice A. Homozygous deletions in parkin gene in European and North African families with autosomal recessive juvenile parkinsonism. The European Consortium on Genetic Susceptibility in Parkinson's Disease and the French Parkinson's Disease Genetics Study Group. Lancet. 352:1998;1355-1356.
27. Leroy E., Anastasopoulos D., Konitsiotis S., Lavedan C., Polymeropoulos M.H. Deletions in the parkin gene and genetic heterogeneity in a Greek family with early-onset Parkinson's disease. Hum Genet. 103:1998;424-427.
28. Nisipeanu P., Inzelberg R., Blumen S.C., Carasso R.L., Hattori N., Matsumine H., Mizuno Y. Autosomal-recessive juvenile parkinsonism in a Jewish Yemenite kindred: mutation of parkin gene. Neurology. 53:1999;1602-1604.
29. Abbas N., Lucking C.B., Ricard S., Durr A., Bonifati V., De Michele G., Bouley S., Vaughan J.R., Gasser T., Marconi R.et al. A wide variety of mutations in the parkin gene are responsible for autosomal recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group and the European Consortium on Genetic Susceptibility in Parkinson's Disease. Hum Mol Genet. 8:1999;567-574. Several novel frameshift, nonsense and missense mutations in the parkin gene, which included heterozygous as well as homozygous point mutations, confirm that a variety of parkin mutations is a more widespread cause of parkinsonism and is not invariably associated with early-onset parkinsonism where in many patients the phenotype is the same as that of idiopathic PD.
30. Harhangi B.S., Oostra B.A., Heutink P., van Duijn C.M., Hofman A., Breteler M.M. N-acetyltransferase-2 polymorphism in Parkinson's disease: the Rotterdam study. J Neurol Neurosurg Psychiatry. 67:1999;518-520.
31. Roses A.D., Strittmatter W.J. Apolipoprotein E and Alzheimer's Disease. Annu Rev Neurosci. 19:1996;53-77.
32. Kruger R., Vieira-Saecker A.M., Kuhn W., Berg D., Muller T., Kuhnl N., Fuchs G.A., Storch A., Hungs M., Woitalla D.et al. Increased susceptibility to sporadic Parkinson's disease by a certain combined alpha-synuclein/apolipoprotein E genotype. Ann Neurol. 45:1999;611-617.
33. Bon M.A., Jansen-Steur E.N., de Vos R.A., Vermes I. Neurogenetic correlates of Parkinson's disease: apolipoprotein-E and cytochrome P450 2D6 genetic polymorphism. Neurosci Lett. 266:1999;149-151.
34. Hutton M., Lendon C.L., Rizzu P., Baker M., Froelich S., Houlden H., Pickering-Brown S., Chakraverty S., Isaacs A., Grover A.et al. Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature. 393:1998;702-705. The widespread incidence of tau fibrillar pathology in several neurodegenerative disorders including Alzheimer's disease and FTDP-17 (frontotemporal dementia with pakinsonism linked to chromosome 17) has for long underlined its importance in these disorders. Abnormal tau aggregation is proposed as a central pathogenic mechanism in these disorders. The discovery of multiple mutations in the tau gene in FTDP-17 has firmly established a role for tau in neurodegeneration. Most mutations affect the tau exon 10 splice sites, thereby causing the inclusion of exon 10 and increase in levels of tau isoforms containing four microtubule-binding repeats.
35. Baker M., Litvan I., Houlden H., Adamson J., Dickson D., Perez-Tur J., Hardy J., Lynch T., Bigio E., Hutton M. Association of an extended haplotype in the tau gene with progressive supranuclear palsy. Hum Mol Genet. 8:1999;711-715. A role of tau in parkinsonism is further supported by the strong association of a particular tau haplotype with PSP.
36. Atkinson A., Singleton A.B., Steward A., Ince P.G., Perry R.H., McKeith I.G., Fairbairn A.F., Edwardson J.A., Daly A.K., Morris C.M. CYP2D6 is associated with Parkinson's disease but not with dementia with Lewy bodies or Alzheimer's disease. Pharmacogenetics. 9:1999;31-35.
37. Stroombergen M.C., Waring R.H. Determination of glutathione S-transferase mu and theta polymorphisms in neurological disease. Hum Exp Toxicol. 18:1999;141-145.
38. Bandmann O., Vaughan J.R., Holmans P., Marsden C.D., Wood N.W. Detailed genotyping demonstrates association between the slow acetylator genotype for N-acetyltransferase 2 (NAT2) and familial Parkinson's disease. Mov Disord. 15:2000;30-35.
39. Mellick G.D., Buchanan D.D., McCann S.J., James K.M., Johnson A.G., Davis D.R., Liyou N., Chan D., Le Couteur D.G. Variations in the monoamine oxidase B (MAOB) gene are associated with Parkinson's disease. Mov Disord. 14:1999;219-224.
40. Satoh J., Kuroda Y. Association of codon 167 Ser/Asn heterozygosity in the parkin gene with sporadic Parkinson's disease. Neuroreport. 10:1999;2735-2739.
41. Wang M., Hattori N., Matsumine H., Kobayashi T., Yoshino H., Morioka A., Kitada T., Asakawa S., Minoshima S., Shimizu N., Mizuno Y. Polymorphism in the parkin gene in sporadic Parkinson's disease. Ann Neurol. 45:1999;655-658.
42. Masliah E., Rockenstein E., Veinbergs I., Mallory M., Hashimoto M., Takeda A., Sagara Y., Sisk A., Mucke L. Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science. 87:2000;1265-1269.
43. Feany M.B., Bender W.W. A Drosophila model of Parkinson's disease. Nature. 404:2000;394-398.
44. Engelender S., Kaminsky Z., Guo X., Sharp A.L., Amaravi R.K., Kleiderlein J.J., Margolis R.L., Troncoso J.C., Lanahan A.A., Worley P.F.et al. Synphilin-1 associates with α-synuclein and promotes the formation of cytosolic inclusions. Nat Genet. 22:1999;110-114.
45. Wakabayashi K., Engelender S., Yoshimoto M., Tsuji S., Ross C.A., Takahashi H. Synphilin-1 is present in Lewy Bodies in Parkinson's disease. Ann Neurol. 47:2000;521-523.