Skip to main content

Protein Structure Modeling of Abnormal Genes Associated with PARK 1 and PARK 8 Loci Related to Autosomal Dominant Parkinson’s Disease and Docking the Protein(s) with Appropriate Ligands

  • Conference paper
  • First Online:
Growth Curve Models and Applications (GCM 2016)

Part of the book series: Springer Proceedings in Mathematics & Statistics ((PROMS,volume 204))

Included in the following conference series:

  • 664 Accesses

Abstract

Parkinson’s disease (PD) is a common neurological disorder with a prevalence of 1–2 per 1000 overall. PD is of two types: autosomal dominant and recessive, autosomal dominant ones are more harmful—than recessive types—and a single copy of their gene causes the disease. Of the five dominant loci involved in PD—PARK1, PARK3, PARK4, PARK5 and PARK8—the two most predominant are PARK1 and PARK8. Understanding and modeling of the abnormal proteins of these genes of the disease is of importance which can help in drug design and help treating patients of PD disease. In this regard, of these five loci, the protein 3-dimensional structure for alpha-synuclein gene present in PARK 1 locus is known but the abnormal alpha-synuclein proteins causing PD is yet to be modeled. However, no 3-D protein structure for PARK 2 gene present PARK8 locus and the abnormal protein coded by the LARK2 gene are not known. And suitable ligands are also not available for these proteins (Dardarin coded by LRRK2 and alpha-synuclein) that can neutralize the effect in the human brain. We report modeling the PARK1 and PARK8 locus abnormal proteins.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Allan W (1937) Inheritance of shaking palsy. Arch Intern Med 60:424–436

    Article  Google Scholar 

  • Andreadis A, Brow MW, Kosik KS (1992) Structure and novel exons of the human \(\tau \) gene. Biochemistry 31:10626–10633

    Article  Google Scholar 

  • Belin AC, Westerlund M (2008) Parkinson’s disease: a genetic perspective. FEBS J 275(7):1377–1383. 10.111/j.1742-4658.2008.06301.x

    Google Scholar 

  • Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, 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 (2003) Mutations in DJ-1 gene associated autosomal recessive early-onset parkinsonism. Science 299(5604):255–259

    Article  Google Scholar 

  • Bowie JU, Luthy R, Eisenberg D (1991) A method to identify protein sequences that fold into a known three-dimensional structure. Science 253(5016):164–170

    Article  Google Scholar 

  • Brice A (2005) How much does dardarin contribute to Parkinson’s disease. Lancet 365(9457):363–364

    Google Scholar 

  • Campion D, Martin C, Heilig R, Charbonnier F, Moreau V, Flaman JM, Petit JL, Hannequin D, Brice A, Frebourg T (1995) The NACP/synuclein gene: chromosomal assignment and screening for alterations in Alzheimer disease. Genomics 26:254–257

    Article  Google Scholar 

  • Chen X, Rohan de Silva HA, Pettenati MJ, Rao PN, St. George-Hyslop P, Roses AD, Xia Y, Horsburgh K, Ueda K, Saitoh, (1995) The human NACP/alpha-synuclein gene: chromosome assignment to 4q21.3-q22 and TaqI RFLP analysis. Genomics 26:425–427

    Google Scholar 

  • Choi HJ, Lee SY, Cho Y, Hwang O (2004) JNK activation by tetrahydrobiopterin: implications for Parkinson’s disease. Neurosci Res 75(5):715–721

    Article  Google Scholar 

  • Christine K, Katja L-H (2007) Impact of recent genetic findings in Parkinson’s disease. Curr Opin Neuro 20(4):453–464

    Article  Google Scholar 

  • Clarimon J, Xiromerisiou G, Eerola J, Gourbali V, Hellstrom O, Dardiotis E, Peuralinna T, Papadimitriou A, Hadjigeorgiou GM, Tienari P, Singleton AB (2005) Lack of evidence for genetic association between FGF20 and Parkinson’s disease in Finnish and Greek patients. BMC Neurol 5:11. doi:10.1186/1471-23775/5/11

    Article  Google Scholar 

  • Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT Jr (2000) 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 97:571–576

    Article  Google Scholar 

  • Cookson MR (2015) LRKK2 pathways leading to neurodegeneration. Curr Neurol Neurosci Rep 15(7):564. doi:10.1007/s11910-015-0564-y

    Article  Google Scholar 

  • Dawson TM, Dawson VL (2003) Molecular pathways of neurodegeneration in Parkinson’s disease. Science 302(5646):819–822. doi:10.1126/science.1087753

    Article  Google Scholar 

  • Day IN, Thompson RJ (1987) Molecular cloning of cDNA coding for human PGP 9.5 protein: a novel cytoplasmic marker for neurones and neuroendocrine cells. Fedrat Europ Biochem Societ Lett (FEBS) 210:157–160

    Article  Google Scholar 

  • Day IN, Hinks LJ, Thompson RJ (1990) The structure of the human gene encoding protein gene product 9.5 (PGP9.5), a neuron-specific ubiquitin C-terminal hydrolase. Biochem J 268(2):521–524. doi:10.1042/bj2680521

  • Dekker MCJ, Bonfati V, van Dujin CM (2003) Parkinson’s disease: piecing together a genetic jigsaw. Brain 126:1722–1733

    Article  Google Scholar 

  • Deng H-X, Shi Y, Yang Y, Kreshnik B, Ahmeti etc. (2016) Identification of TMEM230 mutation in familial Parkinson’s disease. Nat Genet 48(7):733–741

    Google Scholar 

  • Deng J, Lewis PA, Greggio E, Sluch E, Beilina A, Cookson MR (2008) Structure of the ROC domain from the Parkinson’s disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proc Natl Acad Sci 105:1499–1504

    Article  Google Scholar 

  • Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V (2005) Italian Parkinson genetics network : a frequent LRRK2 gene mutation associated with autosomal dominant Parkinson’s disease. Lancet 365:412–415

    Article  Google Scholar 

  • Di Fonzo A, Chien HF, Socal M, Giraudo S, Tassorelli C, Iliceto G, Fabbrini G, Marconi R, Fincati E, Abbruzzese G, Marini P, Squitieri F et al (2007) ATP13A2 missense mutationin juvenile parkinsonism and young onset Parkinson disease. Neurology 87:1557–1562

    Article  Google Scholar 

  • Di Fonzo A, Dekker MC, Montagna R, Baruzzi A, Yonova EH, Correia Guedes L, Szczerbinska A, Zhao T, Dubbel-Hulsman LO, Wouters CH, de Graaff E, Oyen WJ, Simons EJ, Breedveld GJ, Oostra BA, Horstink MW, Bonifati V (2009) FBX07 mutations cause autosomal recessive early-onset parkinsonian-pyramidal syndrome. Neurology 72:240–245

    Article  Google Scholar 

  • Dufty BM, Warner LR, Hou ST, Jiang SX, Gomez-Isla T, Leenhouts KM, Oxford JT, Feany MB, Masliah E, Rohn TT (2007) Calpain-Cleavage of alpha-synuclein: connecting proteolytic processing to disease-linked aggregation. Am J Pathol 170:1725–1738

    Article  Google Scholar 

  • Engelender S, Kaminsky Z, Guo X, Sharp AH, Amaravi RK, Kleiderlein JJ, Margolis RL, Troncoso JC, Lanahan AA, Worley PF, Dawson VL, Dawson TM, Ross CA (1999) Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nat Genet 22:110–114

    Article  Google Scholar 

  • Engelender S, Wanner T, Kleiderlein JJ, Ashworth R, Wakabayashi K, Tsuji S, Takashi H, Margolis RL and Ross CA (2000) Organization of The Human synphilin-1 gene, a candidate for Parkinson’s disease. Mamm Genome 01/09/2000. 11:763-766

    Google Scholar 

  • Erusalimsky JD, Moncada S (2007) Nitric oxide and mitochondrial signaling: from physiology to pathophysiology. Biology 27:2524–2531

    Google Scholar 

  • Faccio L, Fusco C, Chen A, Martinotti S, Bonventre JV, Zervos AS (2000) Characterization of a novel human serine protease that has extensive homology to bacterial heat shock endoprotease HtrA and is regulated by kidney ischemia. J Biol Chem 275:2581–2588

    Article  Google Scholar 

  • Farrer M, Gwinn-Hardy K, Muenter M, DeVrieze FW, Crook R, Perez-Tur J, Lincoln S, Maraganore D, Adler C, Newman S, Mac Elwee K, McCarthy P, Miller C, Waters C, Hardy J (1999) A chromosome 4p haplotypes segregating with Parkinson’s disease and postural tremor. Hum Molec Genet 8:81–85

    Article  Google Scholar 

  • Farrer M, Stone J, Mata IF, Lincoln S, Kachergus J, Hulihan M, Strain KJ, Marganore TM (2005) LRRK2 mutations in Parkinson disease. Neurology 65:738–740. doi:10.1212/01.WNL.0000169023.51764.b0:1526-632x

    Article  Google Scholar 

  • Flower TR, Clark-Dixon C, Metoyer C, Yang H, Shi R, Zhang Z, Witt SN (2007) YGR198w (YPP1) targets A30P alpha-synuclein to the vacuole for degradation. J Cell Biol 177:1091–1104

    Article  Google Scholar 

  • Foround T (2005) LRRK2: both a cause and a risk factor for Parkinson ’s disease? Neurology 65:664–665. doi:10.1212/01.wnl.0000179342.58181.c9

    Article  Google Scholar 

  • Funayama M, Hasegawa K, Ohta E, Kawashima N, Komiyama M, Kowa H, Tsuji S, Obata F (2005) An LRRK2 mutation as a cause for the parkinsonism in the original PARK8 family. Ann Neurol 57:918–921

    Article  Google Scholar 

  • Garnier J, Osguthorpe D, Robson B (1978) Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol 120:97–120

    Article  Google Scholar 

  • Garnier J. JF Gibrat and B Robson (1996) GOR Secondary structure prediction method version IV, In: Doolittle RF (ed) Methods in enzymology, vol 266, pp 540–553

    Google Scholar 

  • Gasser T (2005) Genetics of Parkinson’s disease. Curr Opin Neurol 18:363–369

    Article  Google Scholar 

  • Gasser T, Muller-Myhsok B, Durr Wszolek ZK, Vaughan A, Bonifati JR, Meco V, Bereznai G, Oehlmann B, Agid R, Brice Y, Wood AN (1997) Genetic complexity and Parkinson’s disease. Science 277:388–389

    Google Scholar 

  • Geourjon C, Deleage G (1995) Significant improvement in protein secondary structure prediction by consensus prediction from multiple alignments. Comput Appl Biosci 11(6):681–684

    Google Scholar 

  • Ghosh A, Roy A, Liu X, Kordower JH, Mufson EJ, Hartley DM, Ghosh S, Mosley RL, Gendelman HE, Pahan K (2007) Selective inhibition of NF-kappaB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 104:18754–18759

    Article  Google Scholar 

  • Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP, Lynch J, Healy DG, Holton JL, Revesz T, Wood NW (2005) A common LRRK2 mutation in idiopathic Parkinson’s disease. Lancet 365:415–416

    Google Scholar 

  • Golbe LI, Farrell TM, Davis PH (1990) Follow-up study of early-life protective and risk factors in Parkinson’s disease. Mov Disord 5:66–70

    Article  Google Scholar 

  • Golbe LI, Di Lorio G, Sanges G, Lazzarini AM, La Sala S, Bonavita Duvoisin RC (1996) Clinical genetic analysis of Parkinson’s disease in the Contursi kindred. Ann Neurol 40(5):767–75

    Article  Google Scholar 

  • Goldman JE, Yen S-H, Chiu FC, Peress NS (1983) Lewy bodies of Parkinson’s disease contain neurofilament antigens. Science 83(221):1082–1084

    Article  Google Scholar 

  • Gowers WR, (1900) A manual of diseases of the nervous system. Vol. I. Diseases of the nerves and spinal cord, 3rd edn. P. Blakiston’s Son & Co. pub, Philadelphia

    Google Scholar 

  • Graeber MB, Muller U (1992) The X-linked dystonia-parkinsonism syndrome: clinical and molecular genetic analysis. Brain Pathol 2:287–295

    Article  Google Scholar 

  • Gray CW, Ward RV, Karran E, Turconi S, Rowles A, Viglienghi D, Southan C, Barton A, Fantom KG, West A, Savopoulos J, Hassan NJ, Clinkenbeard H, Hanning C, Amegadzie B, Davis JB, Dingwall C, Livi GP, Creasy CL (2000) Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Europ J Biochem 267:5699–5710

    Article  Google Scholar 

  • Greenbaum EA, Graves CL, Mishizen-Eberz AJ, Lupoli MA, Lynch DR, Englander SW, Axelsen PH, Giasson BI (2005) The E46K mutation in alpha-synuclein increases amyloid fibril formation. J Biol Chem 280:7800–7807

    Article  Google Scholar 

  • Hampshire DJ, Roberts E, Crow Y, Bond J, Mubaidin A, Wriekat AL, Al-Din A, Woods CG (2001) Kufor-Rakeb syndrome, pallid-plyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36. BMJ J Med Genet 38:680–682

    Article  Google Scholar 

  • Hardy Rideout J (ed) (2017) Leucine-rich repeat Kinase 2 (LRRK2). Springer. doi:10.1007/978-3-319-49969-7

  • Hasegawa K, Kowa H (1997) Autosomal dominant familial Parkinson disease: older onset of age, and good response to levodopa therapy. Europ Neurol 38:39–43

    Article  Google Scholar 

  • Health 2012 4(11A) Special issue on Parkinson’s disease

    Google Scholar 

  • Hedrich K, Heintz N, Zoghbi H (1997) Alpha-synuclein–a link between Parkinson and Alzheimer diseases. Nature Genet 16:325–327

    Article  Google Scholar 

  • Hedrich K, Winkler S, Hagenah J, Kabakci K, Kasten M, Schwinger E, Volkmann J, Pramstaller PP, Kostic V, Viergge P, Klein C (2006) Recurrent LRRK2 (Park 8) mutations in early on set of Parkinson’s disease. Movement Disorders 21:1506–1510. doi:10.1002/mds.20990

    Article  Google Scholar 

  • Hedrich K, Marder K, Harris J, Kann M, Lynch T, Mejia-Santana H, Pramstaller PP, Schwinger E, Bressman SB, Fahn S, Klein C (2002) Evaluation of 50 probands with early onset Parkinson’s disease for Parkin mutations. Neurology 58(8):1239–1246. http//dx.doi.org/10.1212/WNL.58.8.1239

    Google Scholar 

  • Hicks AA, Petursson H, Jonsson T, Stefansson H, Johannsdottir HS, Sainz J, Frigge ML, Kong A, Gulcher JR, Stefansson K, Sveinbjornsdottir S (2002) A susceptibility gene for late-onset idiopathic Parkinson’s disease. Ann Neurol 52:549–555

    Article  Google Scholar 

  • Hope AD, Myhre R, Kachergus J, Lincoln S, Bisceglio G, Hulihan M, Farrer MJ (2004) \(\alpha \)-Synuclein missense and multiplication mutations in autosomal dominant Parkinson’s disease. Neurosci Lett 367(1):97–100

    Article  Google Scholar 

  • Jin SM, Youle RJ (2012) PINK1-and Parkin-mediated mitophagy at a glance. J Cell Sci 125:795–799. doi:10.1243/cs.093849

  • Jones DT, Taylort WR, Thomson JM (1992) A new approach to protein fold recognition. Nature 358:86–89. doi:10.1038/358086a0

    Article  Google Scholar 

  • Jun DJ, Kim J, Jung SY, Song R, Noh JH, Park YS, Ryu SH, Kim JH, Kong YY, Chung JM, Kim KT (2007) Extracellular ATP mediates necrotic cell swelling in SN4741 dopaminergic neurons through P2X7 receptors. J Biol Chem 282:37350–37358

    Article  Google Scholar 

  • Kachergus J, Mata IF, Hulihan M, Taylor JP, Lincoln S, Aasly J, Gibson JM, Ross OA, Lynch T, Wiley J, Payami H, Nutt J, Maraganore DM, Czyzewski K, Styczynska M, Wszolek ZK, Farrer MJ, Toft M (2005) Identification of a novel LRRK2 mutation linked to autosomal dominant parkinsonism: evidence of a common founder across European populations. Am J Hum Genet 76:672–680

    Article  Google Scholar 

  • Karamohamed S, DeStefano AL, Wilk JB, Shoemaker CM, Golbe LL, Mark MH, Lazzarini AM, Suchowersky O, Labelle N, Gurrman M, Currie LJ, Wooten GF, 22 others, (2003) A haplotypes at the Park3 locus influences onset age for Parkinson’s disease: the gene PD study. Neurology 61:1557–1561

    Google Scholar 

  • Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608. doi:10.1038/33416

    Article  Google Scholar 

  • Kitada T, Pisani A, Porter DR, Yamaguchi H, Tscherter A, Martella G, Bonsi P, Zhang C, Pothos EN, Shen J (2007) Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice. Proc Natl Acad Sci USA 104:11441–11446

    Article  Google Scholar 

  • Kitada T, Tong Y, Gautier CA, Shen J (2009) Absence of nigral degeneration in aged parkin/DJ-1/PINK1 triple knockout mice. J Neurochem 111:696–702

    Article  Google Scholar 

  • Klein C, Schlossmacher MG (2006) The genetics of Parkinson’s disease: implications for neurological care. Nat Clin Pract Neurol 2:136–146. doi:10.1038/ncpneuro0126

    Article  Google Scholar 

  • Kobayashi M, Kim J, Kobayashi N, Han S, Nakamura C, Ikebukuro K, Sode K (2006) Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein. Biochem Biophys Res Commun 349(3):1139–44

    Article  Google Scholar 

  • Kontakos N, Stokes J (2000) Monograph series on aging-related diseases: XII. Parkinson’s disease-recent developments and new directions. Chronic Diseases 20(3)

    Google Scholar 

  • Kuzuhara S, Mori H, Izumiyama N, Yoshimura M, Ihara Y (1988) Lew bodies are ubiquitinated. Acta Neuropathol 75:345–353

    Article  Google Scholar 

  • Lee LV, Kupke KG, Caballar-Gonzanga F, Hebron-Ortiz M, Muller U (1991) The phenotype of the X-linked dystonia-parkinsonism syndrome. An assessment of 42 cases in the Phyilippines. Medicine 70:179–187

    Article  Google Scholar 

  • Lees AJ, Singleton AW (2007) Clinical heterogeneity of ATP13A2 linked disease (Kufor-Rakeb) justifies a PARK designation. Neurology 68:1553–1554

    Article  Google Scholar 

  • Lennox G, Lowe J, Morrell K, Landon M, Meayer RJ (1989) Anti-ubiquitin immunocyto-chemistry is more sensitive than conventional techniques in the detection of diffuse Levy body disease. J Neurol Neurosurg Psychiatry 52:67–71

    Google Scholar 

  • Leroy E, Boyer R, Polymeropoulos MH (1998) Intron-exon structure of ubiquitin C-terminal hydrolase-L1. DNA Res 5:397–400

    Article  Google Scholar 

  • Lesage S et al (2005) LRRK2 haplotype analyses in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13\(^{th}\) century. Am J Hum Genet 77:330–332

    Article  Google Scholar 

  • Levecque C, Elbaz A, Clavel J, Vidal JS, Amouyel P, Alperovitch A, Tzourio C, Chartier-Harlin MC, (2017) Association of polymorphisms in the Tau and Saitohin genes with Parkinson’s Disease, BMJ: J Neuro Neurosurg Pschiat 75(3):478–480. http://jnnp.bmj.com

  • Li Y, Scott J, Hedges WK, Zhang DJ, Gaskell F, Nance PC, Watts MA, Hubble RL, Koller JP, Pahwa WC, Stern R, Hiner MB (2002) Age at onset in two common neurodegenerative diseases is genetically controlled. Am J Hum Genet 70:985–993

    Article  Google Scholar 

  • Liu C, Fei E, Jia N, Wang H, Tao R, Iwata A, Nukina N, Zhou J, Wang G (2007) Assembly of lysine 63-linked ubiquitin conjugates by phosphorylated alpha-synuclein implies lewy body biogenesis. J Biol Chem 282:14558–14566

    Article  Google Scholar 

  • Massano J, Bhatia KP (2012) Clinical approach to Parkinson’s disease: features, diagnosis and principles of management. Cold Spring Harb Perspect Med 2:a008870. doi:10.1101/cshperspect.a008870

    Article  Google Scholar 

  • Mata IF, Kachergus MJ, Taylor JP, Lincoln S, Aasly J, Lynch T, Hulihan M, Cobb SA, Wu RM, Lu CS, Lahoz C, Wszolek ZK, Farrer JM (2005) LRRK2 pathogenic substitutions in Parkinson’s disease. Neurogenetics 6:171–177

    Article  Google Scholar 

  • Muenter MD, Forno LS, Hornykiewicz O, Kish SJ, Maraganore DM, Casellli RJ, Peuraalinna T, Dutra A, Nusbaum R, Lincoln S, Crawley A, 10 others (1998) Hereditary form of parkinsonism dementia. Ann Neurol 43:768–781

    Google Scholar 

  • Myhre R, Klungland H, Mathew JF, Aasly JO (2008) Genetic association study of synphilin-I in idiopathic Parkinson’s disease. BMC Med Genet 9:19. doi:10.1186/1471-2330-9-19

    Article  Google Scholar 

  • Najim Al-Din AS, Wriekat A, Mubaidin A et al (1994) Pallidopyramidal degeneration, supranuclear upgaze paresis and dementia: Kufor-Rakeb syndrome. Acta Neurol Scand 89:347–352

    Article  Google Scholar 

  • Newhouse Klintworth HK, Li T, Choi W-S, Faigle R, Xia Z (2007) Activation of c- Jun N-terminal protein kinase is a common mechanism underlying Paraquat- and Rotenone-induced dopaminergic cell apoptosis. Toxicol Sci 97:149–162

    Article  Google Scholar 

  • Nichols WC, Pankratz N, Hernandez D, Paisan-Ruiz C, Jain S, Halter CA, Michaels VE, Reed T, Rudolph A, Shults CW, Singleton A, Foroud T (2005) Genetic screening for a single common LRRK2 mutation in familial Parkinson’s disease. Lancet 365:410–412

    Google Scholar 

  • Norris EH, Giasson BI, Lee VM (2004) \(\alpha \)-synuclein: normal function and role in neurodegenerative diseases. Curr Top Dev Biol 60:17–54

    Article  Google Scholar 

  • OMIM #168600, Online Mendelian Inheritance for Man

    Google Scholar 

  • Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Martinez Gil A, Khan N, Johnson J, Martinez JR (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron 44:595–600

    Article  Google Scholar 

  • Paisan-Ruiz C, Lang AE, Kawarai T, Sato C, Salehi-Rad S, Fisman GK, Al-Khairallah T, St P, Singleton George-Hyslop A, Rogaeva E (2005) LRRK2 gene in Parkinson disease: mutation analysis and case control association study. Neurology 65:696–700. doi:10.1212/01.WNL.0000167552.79769.b3:1526-623x

    Article  Google Scholar 

  • Paisan-Ruiz C, Guevara R, Federoff M, Hangasi H, Sina F, Elahi E, Schneider SA, Schwingenschuh P, Bajaj N, Emre M, Singleton AB, Hardy J, Bhatia KP, Brandner S, Lees AJ, Houlden H (2010) Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacism mutations. Mov Disord 25(1):791–800

    Google Scholar 

  • Pankratz N, Nichols WC, Uniacke SK, Halter C, Rudolph A, Shults C, Conneally PM, Foroud T (2002) The Parkinson Study group: genome screen to identify susceptibility genes for Parkinson disease in a sample without parkin mutations. Am J Hum Genet 71:124–135

    Article  Google Scholar 

  • Pankratz N, Nichols WC, Uniacke SK, Halter C, Rudolph A, Shults C, Conneally PM, Foroud T (2003) The Parkinson Study group: significant linkage of Parkinson disease to chromosome 2q36-37. Am J Hum Genet 72:1053–1057

    Article  Google Scholar 

  • Pankratz N, Foroud T (2007) Genetics of Parkinson’s Disease. Genet Med 9(12):801–811

    Article  Google Scholar 

  • Pickrell AM, Youle RJ (2015) The roles of PINK1, Parkin and mitochodrial fidelity in Parkinson’s disease. Neuron 85:257–273

    Article  Google Scholar 

  • Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL (1997) Mutations in the \(\alpha \)-synuclein gene identified in families with Parkinson’s disease. Science 276(5321):2045–2047

    Article  Google Scholar 

  • Polymeropoulos MH, Higgins JJ, Golbe LI, Johnson WG, Ide SE, Di Iorio G, Sanges Gm Stenroos ES, Pho LT, Schaffer AA, Lazzarini AM, Nussbaum RL, Duvoisin RC (1996) Mapping of a gene for Parkinson’s disease to chromosome 4q21-q23. Science 274:1197–1198

    Article  Google Scholar 

  • Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papepetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum R (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276:2045–2047

    Article  Google Scholar 

  • PUBMED. No.: WO/2003/076658, 2003

    Google Scholar 

  • Quian L, Flood PM, Hong J-S (2010) Neuroinflammation is a key player in Parkinson’s disease and a prime target for therapy. J Neural Transm 117(8):971–979

    Article  Google Scholar 

  • Risch N, de Leon D, Ozelius L, Kramer P, Almasy L, Singer B, Fahn S, Breakefield X, Bresman S (1995) Genetic analysis of idiopathic dystonia in Askenazi Jews and their recent descent from a small founder population. Nat Genet 9:152–159. doi:10.1038/ng0295-152

    Article  Google Scholar 

  • Ritchie CM, Thomas PJ (2012) Alpha-synuclein truncation and disease. Health 4(11A):1167–1177

    Article  Google Scholar 

  • Schmidt ML, Murray J, Lee VM-Y, Hill MD, Trojanowski JQ (1991) Epitope map of neurofilament protein domains in cortical and peripheral nervous Lewy bodies. Am J Pathol 139:53–65

    Google Scholar 

  • Scott WK, Stajich JM, Yamaoka LH, Speer MC, Vance JM, Roses AD, Pericak-Vance MA, Deane Laboratory Parkinson Disease Research Group (1997) Genetic complexity and Parkinson’s disease. Science 277:387–388

    Article  Google Scholar 

  • Scott WK, Nance MA, Watts RL, Hubble JP, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic J (2001) Complete genomic screen in Parkinson disease: evidence for multiple genes. JAMA 286:2239–2244

    Article  Google Scholar 

  • Scott L, Dawson VL, Dawson T (2017) Trumping neurodegeneration: targeting common pathways regulated by autosomal recessive Parkinson’s disease genes. Exp Neurol (in press). doi:10.1016/j.expneurol.2017.04.008

    Google Scholar 

  • Shibasaki Y, Baillie DAM, St Clair D, Brookes AJ (1995) High-resolution mapping of SNCA encoding a-synuclein, the non-A-beta component of Alzheimer’s disease amyloid precursor, to human chromosome 4q21.3-q22 by fluorescence in situ hybridization. Cytogenet Cell Genet 71:54–55

    Article  Google Scholar 

  • Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M (2003) Alpha-synuclein locus triplication causes Parkinson’s disease. Science 302:841. doi:10.1126/science.1090278

    Article  Google Scholar 

  • Spillantini MG, Divane A, Goedert M (1995) Assignment of human alpha-synuclein (SNCA) and beta-synuclein (SNCB) genes to chromosomes 4q21 and 5q35. Genomics 27:379–381

    Article  Google Scholar 

  • Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M (1997) \(\alpha \)-synuclein in lewy bodies. Nature 388:839–840

    Article  Google Scholar 

  • Sredni B, Geffen-Aricha R, Duan W, Albeck M, Shalit F, Lander HM, Kinor N, Sagi O, Albeck A, Yosef S et al (2007) Multifunctional tellurium molecule protects and restores dopaminergic neurons in Parkinson’s disease models. FASEB J 21:1870–1883

    Article  Google Scholar 

  • Stevenin G, Cancel G, Didierjean O, Durr A, Abbas N, Cassa E, Feingold J, Agid Y, Brice A (1995) Linkage disequilibrium at the Machado-Joseph disease/spinal cerebellar ataxia 3 locus: evidence for a common founder effect in French and Portuguese_Brazillian families as a second ancestral Portuguese-Azorean mutation. Am J Hum Genet 57:1247–1250

    Google Scholar 

  • Tan LCS, Venketasubramanian N, Hong CY, Sahadevan S, Chin JJ, Krishnamoorthy ES, Tan AKY, Saw SM (2004) Prevalence of Parkinson disease in Singapore: Chinese vs Malays vs Indians. Neurology 62:1999–2004

    Article  Google Scholar 

  • Toft M, Mata IF, Kachergus JM, Ross OA, Farrer MJ (2005) LRRK2 mutations and Parkinsonism. Lancet 365(9466):1229–30

    Article  Google Scholar 

  • Trenkwalder C, Schwarz J, Gebhard J, Ruland D, Trenkwalder P, Hense HW, Oertel WH (1995) Starnberg trial on epidemiology of Parkinsonism and hypertension in the elderly: prevalence of Parkinson’s disease and related disorders assessed by a door-to-door survey of inhabitants older than 65 years. Arch Neurol 52:1017–1022

    Article  Google Scholar 

  • Ueffing M, Meitinger T, Gasser T, Farrer MJ et al (2008) Helmholtz Zentrum München. University Clinic Tübingen, Mayo Clinic, BioVaria

    Google Scholar 

  • Valente EM, Caputo Abou-Sleiman PM, V, Mugit MMK, Harvey K, et al (2004) Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science 304(1158):1160. doi:10.1126/science.1096284

  • Valente EM, Bentivoglio AR, Dixon PH, Ferraris A, Ialongo T, Frontali M, Albanese A, Wood NW (2001) Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36. Am J Hum Genet 68:895–900

    Article  Google Scholar 

  • Van Duijn CM, Dekker MCJ, Bonifati V, Galjaard RJ, Houwing-Duistermaat JJ, Snijders PJLM, Testers L, Breedveld GJ, Horstink M, Sandkuijl LA, Van Swieten JC, Oostra BA, Heutink P (2001) PARK7, a novel locus for autosomal recessive early-onset parkinsonism, on chromosome 1p36. Am J Hum Genet 69:629–634

    Article  Google Scholar 

  • Wassef R, Haenold R, Hansel A, Brot N, Heinemann SH, Hoshi T (2007) Methionine Sulfoxide Reductase A and a Dietary Supplement S-Methyl-L- Cysteine Prevent Parkinson’s-Like Symptoms. J Neurosci 27:12808–12816

    Article  Google Scholar 

  • Watabe M, Nakaki T (2007) Mitochondrial Complex I Inhibitor Rotenone-Elicited Dopamine Redistribution from Vesicles to Cytosol in Human Dopaminergic SH- SY5Y Cells. J Pharmacol Exp Ther 323:499–507. doi:10.1124/jpet.107.128017

    Article  Google Scholar 

  • Waters CH, Miller CA (1994) Autosomal dominant Lewy body parkinsonism in a four generation family. Ann Neurol 35:59–64

    Article  Google Scholar 

  • Wellenbrock CK Hedrich, N Schafer, M Kasten, H Jacob, E Schwinger, J Hagenah, PP Pramstaller, P Vieregge, C Klein (2003) NR4A2 mutations are rare among European patients with familial Parkinson’s disease. Ann Neruol 54(3):415- PMD:12953278, DOI:1002/ana.10738

    Google Scholar 

  • West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci 102:16842–16847

    Article  Google Scholar 

  • Wirdefeldt K, Gatz M, Schalling M, Pedersen NL (2004) No evidence for heritability of Parkinson disease in Swedish twins. Neurology 63:305–311

    Article  Google Scholar 

  • Wszolek ZK et al (2004) Autosomal dominant Parkinsonism associated with variable synuclein and tau pathology. Neurology 62:1619–1622

    Article  Google Scholar 

  • Wszolek ZK, Vieregge P, Uitti RJ, Gasser T, Yasuhara O, McGeer P, Berry K, Calne DB, Vingerhoets FJG, Klein C, Pfeiffer RF (1997) German-Canadian family (family A) with parkinsonism, amyotrophy, and dementia-longitudinal observations. Parkinsonism Relat Disord 3:125–139

    Article  Google Scholar 

  • Xiong M, Guo SW (1997) Fine-scale genetic mapping based on linkage disequilibrium: theory and applications. Am J Hum Genet 60:1513–1531

    Article  Google Scholar 

  • Xiong Y, Dawson TM, Dawson VL (2017) Models of LRRK2-associated Parkinson’s disease. In: Rideout HJ (ed) Advances in neurobiology, Leucine-Rich Repeat Kinase 2 (LRRK2). Springer, pp 163–191

    Google Scholar 

  • Zabetian CP, Samii A, Mosley AD, Roberts JW, Leis BC, Yearout D, Raskind WH, Griffith A (2005) A clinic-based study of the LRRK2 gene in Parkinson disease yields new mutations. Neurology 65(5):741–744. doi:10.1212/01.WNL.0000172630.22804.73:1526-632x

    Article  Google Scholar 

  • Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG (2004) The new mutation, E46K, of alpha-synuclein causes parkinson and Lewy body dementia. Ann Neurol 55:164–173

    Article  Google Scholar 

  • Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carballo Carbajal I, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601–607

    Google Scholar 

Web References

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. S. Vasulu .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this paper

Cite this paper

Roy, S., Vasulu, T.S. (2017). Protein Structure Modeling of Abnormal Genes Associated with PARK 1 and PARK 8 Loci Related to Autosomal Dominant Parkinson’s Disease and Docking the Protein(s) with Appropriate Ligands. In: Dasgupta, R. (eds) Growth Curve Models and Applications. GCM 2016. Springer Proceedings in Mathematics & Statistics, vol 204. Springer, Cham. https://doi.org/10.1007/978-3-319-63886-7_2

Download citation

Publish with us

Policies and ethics