Abstract
Parkinson's disease and Huntington's disease are both model diseases. Parkinson's disease is the most common of several akinetic-rigid syndromes and Huntington's disease is only one of an ever growing number of trinucleotide repeat disorders. Molecular genetic studies and subsequent molecular biological studies have provided fascinating new insights into the pathogenesis of both disorders and there is now real hope for disease modifying treatment in the not too distant future for patients with Parkinson's disease or Huntington's disease.
Full Text
The Full Text of this article is available as a PDF (110.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abeliovich A., Schmitz Y., Fariñas I., Choi-Lundberg D., Ho W. H., Castillo P. E., Shinsky N., Verdugo J. M., Armanini M., Ryan A. Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron. 2000 Jan;25(1):239–252. doi: 10.1016/s0896-6273(00)80886-7. [DOI] [PubMed] [Google Scholar]
- Alves da Costa C. Recent advances on alpha-synuclein cell biology: functions and dysfunctions. Curr Mol Med. 2003 Feb;3(1):17–24. doi: 10.2174/1566524033361690. [DOI] [PubMed] [Google Scholar]
- Andreassen O. A., Dedeoglu A., Ferrante R. J., Jenkins B. G., Ferrante K. L., Thomas M., Friedlich A., Browne S. E., Schilling G., Borchelt D. R. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol Dis. 2001 Jun;8(3):479–491. doi: 10.1006/nbdi.2001.0406. [DOI] [PubMed] [Google Scholar]
- Arrasate Montserrat, Mitra Siddhartha, Schweitzer Erik S., Segal Mark R., Finkbeiner Steven. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature. 2004 Oct 14;431(7010):805–810. doi: 10.1038/nature02998. [DOI] [PubMed] [Google Scholar]
- Auluck Pavan K., Meulener Marc C., Bonini Nancy M. Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila. J Biol Chem. 2004 Nov 18;280(4):2873–2878. doi: 10.1074/jbc.M412106200. [DOI] [PubMed] [Google Scholar]
- Betarbet R., Sherer T. B., MacKenzie G., Garcia-Osuna M., Panov A. V., Greenamyre J. T. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci. 2000 Dec;3(12):1301–1306. doi: 10.1038/81834. [DOI] [PubMed] [Google Scholar]
- Bonifati Vincenzo, Breedveld Guido J., Squitieri Ferdinando, Vanacore Nicola, Brustenghi Pierluigi, Harhangi Biswadjiet S., Montagna Pasquale, Cannella Milena, Fabbrini Giovanni, Rizzu Patrizia. Localization of autosomal recessive early-onset parkinsonism to chromosome 1p36 (PARK7) in an independent dataset. Ann Neurol. 2002 Feb;51(2):253–256. doi: 10.1002/ana.10106. [DOI] [PubMed] [Google Scholar]
- Cattaneo E., Rigamonti D., Goffredo D., Zuccato C., Squitieri F., Sipione S. Loss of normal huntingtin function: new developments in Huntington's disease research. Trends Neurosci. 2001 Mar;24(3):182–188. doi: 10.1016/s0166-2236(00)01721-5. [DOI] [PubMed] [Google Scholar]
- Ciechanover A., Orian A., Schwartz A. L. The ubiquitin-mediated proteolytic pathway: mode of action and clinical implications. J Cell Biochem Suppl. 2000;34:40–51. doi: 10.1002/(sici)1097-4644(2000)77:34+<40::aid-jcb9>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
- Dauer William, Kholodilov Nikolai, Vila Miquel, Trillat Anne-Cecile, Goodchild Rose, Larsen Kristin E., Staal Roland, Tieu Kim, Schmitz Yvonne, Yuan Chao Annie. Resistance of alpha -synuclein null mice to the parkinsonian neurotoxin MPTP. Proc Natl Acad Sci U S A. 2002 Oct 10;99(22):14524–14529. doi: 10.1073/pnas.172514599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dawson Ted M., Dawson Valina L. Rare genetic mutations shed light on the pathogenesis of Parkinson disease. J Clin Invest. 2003 Jan;111(2):145–151. doi: 10.1172/JCI17575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Di Fonzo Alessio, Rohé Christan F., Ferreira Joaquim, Chien Hsin F., Vacca Laura, Stocchi Fabrizio, Guedes Leonor, Fabrizio Edito, Manfredi Mario, Vanacore Nicola. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. 2005 Jan 29-Feb 4Lancet. 365(9457):412–415. doi: 10.1016/S0140-6736(05)17829-5. [DOI] [PubMed] [Google Scholar]
- Dunah Anthone W., Jeong Hyunkyung, Griffin April, Kim Yong-Man, Standaert David G., Hersch Steven M., Mouradian M. Maral, Young Anne B., Tanese Naoko, Krainc Dimitri. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science. 2002 May 2;296(5576):2238–2243. doi: 10.1126/science.1072613. [DOI] [PubMed] [Google Scholar]
- Farrer M., Maraganore D. M., Lockhart P., Singleton A., Lesnick T. G., de Andrade M., West A., de Silva R., Hardy J., Hernandez D. alpha-Synuclein gene haplotypes are associated with Parkinson's disease. Hum Mol Genet. 2001 Aug 15;10(17):1847–1851. doi: 10.1093/hmg/10.17.1847. [DOI] [PubMed] [Google Scholar]
- Farrer M., Maraganore D. M., Lockhart P., Singleton A., Lesnick T. G., de Andrade M., West A., de Silva R., Hardy J., Hernandez D. alpha-Synuclein gene haplotypes are associated with Parkinson's disease. Hum Mol Genet. 2001 Aug 15;10(17):1847–1851. doi: 10.1093/hmg/10.17.1847. [DOI] [PubMed] [Google Scholar]
- Gao Hui-Ming, Hong Jau-Shyong, Zhang Wanqin, Liu Bin. Synergistic dopaminergic neurotoxicity of the pesticide rotenone and inflammogen lipopolysaccharide: relevance to the etiology of Parkinson's disease. J Neurosci. 2003 Feb 15;23(4):1228–1236. doi: 10.1523/JNEUROSCI.23-04-01228.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gilks William P., Abou-Sleiman Patrick M., Gandhi Sonia, Jain Shushant, Singleton Andrew, Lees Andrew J., Shaw Karen, Bhatia Kailash P., Bonifati Vincenzo, Quinn Niall P. A common LRRK2 mutation in idiopathic Parkinson's disease. 2005 Jan 29-Feb 4Lancet. 365(9457):415–416. doi: 10.1016/S0140-6736(05)17830-1. [DOI] [PubMed] [Google Scholar]
- Golbe L. I., Di Iorio G., Sanges G., Lazzarini A. M., La Sala S., Bonavita V., Duvoisin R. C. Clinical genetic analysis of Parkinson's disease in the Contursi kindred. Ann Neurol. 1996 Nov;40(5):767–775. doi: 10.1002/ana.410400513. [DOI] [PubMed] [Google Scholar]
- Hague Stephen, Rogaeva Ekaterina, Hernandez Dena, Gulick Cindy, Singleton Amanda, Hanson Melissa, Johnson Janel, Weiser Roberto, Gallardo Marisol, Ravina Bernard. Early-onset Parkinson's disease caused by a compound heterozygous DJ-1 mutation. Ann Neurol. 2003 Aug;54(2):271–274. doi: 10.1002/ana.10663. [DOI] [PubMed] [Google Scholar]
- Healy Daniel G., Abou-Sleiman Patrick M., Ahmadi Kourosh R., Muqit Miratul M. K., Bhatia Kailash P., Quinn Niall P., Lees Andrew J., Latchmann David S., Goldstein David B., Wood Nicholas W. The gene responsible for PARK6 Parkinson's disease, PINK1, does not influence common forms of parkinsonism. Ann Neurol. 2004 Sep;56(3):329–335. doi: 10.1002/ana.20206. [DOI] [PubMed] [Google Scholar]
- Hughes R. E., Olson J. M. Therapeutic opportunities in polyglutamine disease. Nat Med. 2001 Apr;7(4):419–423. doi: 10.1038/86486. [DOI] [PubMed] [Google Scholar]
- Hughes Robert E. Polyglutamine disease: acetyltransferases awry. Curr Biol. 2002 Feb 19;12(4):R141–R143. doi: 10.1016/s0960-9822(02)00709-1. [DOI] [PubMed] [Google Scholar]
- Höglinger Günter U., Féger Jean, Prigent Annick, Michel Patrick P., Parain Karine, Champy Pierre, Ruberg Merle, Oertel Wolfgang H., Hirsch Etienne C. Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats. J Neurochem. 2003 Feb;84(3):491–502. doi: 10.1046/j.1471-4159.2003.01533.x. [DOI] [PubMed] [Google Scholar]
- Jana N. R., Zemskov E. A., Wang Gh, Nukina N. Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release. Hum Mol Genet. 2001 May 1;10(10):1049–1059. doi: 10.1093/hmg/10.10.1049. [DOI] [PubMed] [Google Scholar]
- Khan N., Graham E., Dixon P., Morris C., Mander A., Clayton D., Vaughan J., Quinn N., Lees A., Daniel S. Parkinson's disease is not associated with the combined alpha-synuclein/apolipoprotein E susceptibility genotype. Ann Neurol. 2001 May;49(5):665–668. [PubMed] [Google Scholar]
- Khan Naheed L., Brooks David J., Pavese Nicola, Sweeney Mary G., Wood Nicholas W., Lees Andrew J., Piccini Paola. Progression of nigrostriatal dysfunction in a parkin kindred: an [18F]dopa PET and clinical study. Brain. 2002 Oct;125(Pt 10):2248–2256. doi: 10.1093/brain/awf237. [DOI] [PubMed] [Google Scholar]
- Kirik Deniz, Annett Lucy E., Burger Corinna, Muzyczka Nicholas, Mandel Ronald J., Björklund Anders. Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson's disease. Proc Natl Acad Sci U S A. 2003 Feb 24;100(5):2884–2889. doi: 10.1073/pnas.0536383100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klein C., Pramstaller P. P., Kis B., Page C. C., Kann M., Leung J., Woodward H., Castellan C. C., Scherer M., Vieregge P. Parkin deletions in a family with adult-onset, tremor-dominant parkinsonism: expanding the phenotype. Ann Neurol. 2000 Jul;48(1):65–71. [PubMed] [Google Scholar]
- Kobayashi Hirokazu, Krüger Rejko, Markopoulou Katerina, Wszolek Zbigniew, Chase Bruce, Taka Hikaru, Mineki Reiko, Murayama Kimie, Riess Olaf, Mizuno Yoshikuni. Haploinsufficiency at the alpha-synuclein gene underlies phenotypic severity in familial Parkinson's disease. Brain. 2003 Jan;126(Pt 1):32–42. doi: 10.1093/brain/awg010. [DOI] [PubMed] [Google Scholar]
- Krüger R., Kuhn W., Leenders K. L., Sprengelmeyer R., Müller T., Woitalla D., Portman A. T., Maguire R. P., Veenma L., Schröder U. Familial parkinsonism with synuclein pathology: clinical and PET studies of A30P mutation carriers. Neurology. 2001 May 22;56(10):1355–1362. doi: 10.1212/wnl.56.10.1355. [DOI] [PubMed] [Google Scholar]
- Krüger R., Kuhn W., Müller T., Woitalla D., Graeber M., Kösel S., Przuntek H., Epplen J. T., Schöls L., Riess O. Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson's disease. Nat Genet. 1998 Feb;18(2):106–108. doi: 10.1038/ng0298-106. [DOI] [PubMed] [Google Scholar]
- Krüger R., Vieira-Saecker A. M., Kuhn W., Berg D., Müller T., Kühnl N., Fuchs G. A., Storch A., Hungs M., Woitalla D. Increased susceptibility to sporadic Parkinson's disease by a certain combined alpha-synuclein/apolipoprotein E genotype. Ann Neurol. 1999 May;45(5):611–617. doi: 10.1002/1531-8249(199905)45:5<611::aid-ana9>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
- Kuroda Y., Mitsui T., Akaike M., Azuma H., Matsumoto T. Homozygous deletion mutation of the parkin gene in patients with atypical parkinsonism. J Neurol Neurosurg Psychiatry. 2001 Aug;71(2):231–234. doi: 10.1136/jnnp.71.2.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lansbury Peter T., Jr, Brice Alexis. Genetics of Parkinson's disease and biochemical studies of implicated gene products. Curr Opin Cell Biol. 2002 Oct;14(5):653–660. doi: 10.1016/s0955-0674(02)00377-0. [DOI] [PubMed] [Google Scholar]
- Leroy E., Boyer R., Auburger G., Leube B., Ulm G., Mezey E., Harta G., Brownstein M. J., Jonnalagada S., Chernova T. The ubiquitin pathway in Parkinson's disease. Nature. 1998 Oct 1;395(6701):451–452. doi: 10.1038/26652. [DOI] [PubMed] [Google Scholar]
- Lücking C. B., Dürr A., Bonifati V., Vaughan J., De Michele G., Gasser T., Harhangi B. S., Meco G., Denèfle P., Wood N. W. Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med. 2000 May 25;342(21):1560–1567. doi: 10.1056/NEJM200005253422103. [DOI] [PubMed] [Google Scholar]
- Maraganore D. M., Farrer M. J., Hardy J. A., Lincoln S. J., McDonnell S. K., Rocca W. A. Case-control study of the ubiquitin carboxy-terminal hydrolase L1 gene in Parkinson's disease. Neurology. 1999 Nov 10;53(8):1858–1860. doi: 10.1212/wnl.53.8.1858. [DOI] [PubMed] [Google Scholar]
- Maraganore D. M., Wilkes K., Lesnick T. G., Strain K. J., de Andrade M., Rocca W. A., Bower J. H., Ahlskog J. E., Lincoln S., Farrer M. J. A limited role for DJ1 in Parkinson disease susceptibility. Neurology. 2004 Aug 10;63(3):550–553. doi: 10.1212/01.wnl.0000133402.78621.ad. [DOI] [PubMed] [Google Scholar]
- McCormack Alison L., Thiruchelvam Mona, Manning-Bog Amy B., Thiffault Christine, Langston J. William, Cory-Slechta Deborah A., Di Monte Donato A. Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis. 2002 Jul;10(2):119–127. doi: 10.1006/nbdi.2002.0507. [DOI] [PubMed] [Google Scholar]
- McLean P. J., Kawamata H., Hyman B. T. Alpha-synuclein-enhanced green fluorescent protein fusion proteins form proteasome sensitive inclusions in primary neurons. Neuroscience. 2001;104(3):901–912. doi: 10.1016/s0306-4522(01)00113-0. [DOI] [PubMed] [Google Scholar]
- McNaught Kevin St P., Belizaire Roger, Isacson Ole, Jenner Peter, Olanow C. Warren. Altered proteasomal function in sporadic Parkinson's disease. Exp Neurol. 2003 Jan;179(1):38–46. doi: 10.1006/exnr.2002.8050. [DOI] [PubMed] [Google Scholar]
- McNaught Kevin St P., Perl Daniel P., Brownell Anna-Liisa, Olanow C. Warren. Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease. Ann Neurol. 2004 Jul;56(1):149–162. doi: 10.1002/ana.20186. [DOI] [PubMed] [Google Scholar]
- Miller David W., Ahmad Rili, Hague Stephen, Baptista Melisa J., Canet-Aviles Rosa, McLendon Chris, Carter Donald M., Zhu Peng-Peng, Stadler Julia, Chandran Jayanth. L166P mutant DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitin-proteasome system. J Biol Chem. 2003 Jul 8;278(38):36588–36595. doi: 10.1074/jbc.M304272200. [DOI] [PubMed] [Google Scholar]
- Muchowski Paul J. Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones? Neuron. 2002 Jul 3;35(1):9–12. doi: 10.1016/s0896-6273(02)00761-4. [DOI] [PubMed] [Google Scholar]
- Neumann Manuela, Müller Veronika, Görner Karin, Kretzschmar Hans A., Haass Christian, Kahle Philipp J. Pathological properties of the Parkinson's disease-associated protein DJ-1 in alpha-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick's disease. Acta Neuropathol. 2004 Feb 26;107(6):489–496. doi: 10.1007/s00401-004-0834-2. [DOI] [PubMed] [Google Scholar]
- Nichols William C., Pankratz Nathan, Hernandez Dena, Paisán-Ruíz Coro, Jain Shushant, Halter Cheryl A., Michaels Veronika E., Reed Terry, Rudolph Alice, Shults Clifford W. Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease. 2005 Jan 29-Feb 4Lancet. 365(9457):410–412. doi: 10.1016/S0140-6736(05)17828-3. [DOI] [PubMed] [Google Scholar]
- Orr C. F., Rowe D. B., Halliday G. M. An inflammatory review of Parkinson's disease. Prog Neurobiol. 2002 Dec;68(5):325–340. doi: 10.1016/s0301-0082(02)00127-2. [DOI] [PubMed] [Google Scholar]
- Paisán-Ruíz Coro, Jain Shushant, Evans E. Whitney, Gilks William P., Simón Javier, van der Brug Marcel, López de Munain Adolfo, Aparicio Silvia, Gil Angel Martínez, Khan Naheed. Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron. 2004 Nov 18;44(4):595–600. doi: 10.1016/j.neuron.2004.10.023. [DOI] [PubMed] [Google Scholar]
- Papp M. I., Kahn J. E., Lantos P. L. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci. 1989 Dec;94(1-3):79–100. doi: 10.1016/0022-510x(89)90219-0. [DOI] [PubMed] [Google Scholar]
- Polymeropoulos M. H., Lavedan C., Leroy E., Ide S. E., Dehejia A., Dutra A., Pike B., Root H., Rubenstein J., Boyer R. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997 Jun 27;276(5321):2045–2047. doi: 10.1126/science.276.5321.2045. [DOI] [PubMed] [Google Scholar]
- Rizzu Patrizia, Hinkle David A., Zhukareva Victoria, Bonifati Vincenzo, Severijnen Lies-Anne, Martinez Daniel, Ravid Rivka, Kamphorst Wouter, Eberwine James H., Lee Virginia M-Y. DJ-1 colocalizes with tau inclusions: a link between parkinsonism and dementia. Ann Neurol. 2004 Jan;55(1):113–118. doi: 10.1002/ana.10782. [DOI] [PubMed] [Google Scholar]
- Rohé Christan F., Montagna Pasquale, Breedveld Guido, Cortelli Pietro, Oostra Ben A., Bonifati Vincenzo. Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism. Ann Neurol. 2004 Sep;56(3):427–431. doi: 10.1002/ana.20247. [DOI] [PubMed] [Google Scholar]
- Ross Christopher A., Poirier Michelle A., Wanker Erich E., Amzel Mario. Polyglutamine fibrillogenesis: the pathway unfolds. Proc Natl Acad Sci U S A. 2002 Dec 30;100(1):1–3. doi: 10.1073/pnas.0237018100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schrag A., Ben-Shlomo Y., Quinn N. P. Cross sectional prevalence survey of idiopathic Parkinson's disease and Parkinsonism in London. BMJ. 2000 Jul 1;321(7252):21–22. doi: 10.1136/bmj.321.7252.21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seo Hyemyung, Sonntag Kai-Christian, Isacson Ole. Generalized brain and skin proteasome inhibition in Huntington's disease. Ann Neurol. 2004 Sep;56(3):319–328. doi: 10.1002/ana.20207. [DOI] [PubMed] [Google Scholar]
- Singleton A. B., Farrer M., Johnson J., Singleton A., Hague S., Kachergus J., Hulihan M., Peuralinna T., Dutra A., Nussbaum R. alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003 Oct 31;302(5646):841–841. doi: 10.1126/science.1090278. [DOI] [PubMed] [Google Scholar]
- Smith Donna L., Woodman Benjamin, Mahal Amarbirpal, Sathasivam Kirupa, Ghazi-Noori Shabnam, Lowden Philip A. S., Bates Gillian P., Hockly Emma. Minocycline and doxycycline are not beneficial in a model of Huntington's disease. Ann Neurol. 2003 Aug;54(2):186–196. doi: 10.1002/ana.10614. [DOI] [PubMed] [Google Scholar]
- Souza J. M., Giasson B. I., Chen Q., Lee V. M., Ischiropoulos H. Dityrosine cross-linking promotes formation of stable alpha -synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J Biol Chem. 2000 Jun 16;275(24):18344–18349. doi: 10.1074/jbc.M000206200. [DOI] [PubMed] [Google Scholar]
- Spira P. J., Sharpe D. M., Halliday G., Cavanagh J., Nicholson G. A. Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation. Ann Neurol. 2001 Mar;49(3):313–319. [PubMed] [Google Scholar]
- Squitieri Ferdinando, Gellera Cinzia, Cannella Milena, Mariotti Caterina, Cislaghi Giuliana, Rubinsztein David C., Almqvist Elisabeth W., Turner David, Bachoud-Lévi Anne-Catherine, Simpson Sheila A. Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course. Brain. 2003 Apr;126(Pt 4):946–955. doi: 10.1093/brain/awg077. [DOI] [PubMed] [Google Scholar]
- Stefanis L., Larsen K. E., Rideout H. J., Sulzer D., Greene L. A. Expression of A53T mutant but not wild-type alpha-synuclein in PC12 cells induces alterations of the ubiquitin-dependent degradation system, loss of dopamine release, and autophagic cell death. J Neurosci. 2001 Dec 15;21(24):9549–9560. doi: 10.1523/JNEUROSCI.21-24-09549.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sánchez Ivelisse, Mahlke Christian, Yuan Junying. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature. 2003 Jan 23;421(6921):373–379. doi: 10.1038/nature01301. [DOI] [PubMed] [Google Scholar]
- Teismann Peter, Tieu Kim, Choi Dong-Kug, Wu Du-Chu, Naini Ali, Hunot Stéphane, Vila Miquel, Jackson-Lewis Vernice, Przedborski Serge. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc Natl Acad Sci U S A. 2003 Apr 17;100(9):5473–5478. doi: 10.1073/pnas.0837397100. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Temussi Piero Andrea, Masino Laura, Pastore Annalisa. From Alzheimer to Huntington: why is a structural understanding so difficult? EMBO J. 2003 Feb 3;22(3):355–361. doi: 10.1093/emboj/cdg044. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Valente Enza Maria, Abou-Sleiman Patrick M., Caputo Viviana, Muqit Miratul M. K., Harvey Kirsten, Gispert Suzana, Ali Zeeshan, Del Turco Domenico, Bentivoglio Anna Rita, Healy Daniel G. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004 Apr 15;304(5674):1158–1160. doi: 10.1126/science.1096284. [DOI] [PubMed] [Google Scholar]
- West Andrew B., Maraganore Demetrius, Crook Julia, Lesnick Tim, Lockhart Paul J., Wilkes Kristen M., Kapatos Gregory, Hardy John A., Farrer Matt J. Functional association of the parkin gene promoter with idiopathic Parkinson's disease. Hum Mol Genet. 2002 Oct 15;11(22):2787–2792. doi: 10.1093/hmg/11.22.2787. [DOI] [PubMed] [Google Scholar]
- Xu Jin, Kao Shyan-Yuan, Lee Frank J. S., Song Weihong, Jin Lee-Way, Yankner Bruce A. Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med. 2002 Jun;8(6):600–606. doi: 10.1038/nm0602-600. [DOI] [PubMed] [Google Scholar]
- Yamada Masanori, Mizuno Yoshikuni, Mochizuki Hideki. Parkin gene therapy for alpha-synucleinopathy: a rat model of Parkinson's disease. Hum Gene Ther. 2005 Feb;16(2):262–270. doi: 10.1089/hum.2005.16.262. [DOI] [PubMed] [Google Scholar]
- Yokota Takanori, Sugawara Kanako, Ito Kaoru, Takahashi Ryosuke, Ariga Hiroyoshi, Mizusawa Hidehiro. Down regulation of DJ-1 enhances cell death by oxidative stress, ER stress, and proteasome inhibition. Biochem Biophys Res Commun. 2003 Dec 26;312(4):1342–1348. doi: 10.1016/j.bbrc.2003.11.056. [DOI] [PubMed] [Google Scholar]
- Zarranz Juan J., Alegre Javier, Gómez-Esteban Juan C., Lezcano Elena, Ros Raquel, Ampuero Israel, Vidal Lídice, Hoenicka Janet, Rodriguez Olga, Atarés Begoña. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004 Feb;55(2):164–173. doi: 10.1002/ana.10795. [DOI] [PubMed] [Google Scholar]
- Zimprich Alexander, Biskup Saskia, Leitner Petra, Lichtner Peter, Farrer Matthew, Lincoln Sarah, Kachergus Jennifer, Hulihan Mary, Uitti Ryan J., Calne Donald B. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004 Nov 18;44(4):601–607. doi: 10.1016/j.neuron.2004.11.005. [DOI] [PubMed] [Google Scholar]
