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Biopterin levels in the cerebrospinal fluid of patients with PARK8 (I2020T)

  • Basic Neurosciences, Genetics and Immunology - Short Communication
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Abstract

PARK8 is the most common form of familial Parkinson’s disease (PD). We measured biopterin and monoamine metabolite levels in the cerebrospinal fluids of 7 PARK8 patients (I2020T mutation in leucine-rich repeat kinase 2), 2 asymptomatic mutation carriers, and 21 sporadic PD patients. The biopterin levels in PARK8 patients were significantly higher than those in sporadic PD patients, although the symptoms were comparable in both groups, suggesting that PARK8 patients exhibit parkinsonian symptoms with higher biopterin levels than sporadic PD patients.

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References

  • Adams JR, van Netten H, Schulzer M, Mak E, McKenzie J, Strongosky A, Sossi V, Ruth TJ, Lee CS, Farrer M, Gasser T, Uitti RJ, Calne DB, Wszolek ZK, Stoessl AJ (2005) PET in LRRK2 mutations: comparison to sporadic Parkinson’s disease and evidence for presymptomatic compensation. Brain 128:2777–2785

    Article  PubMed  Google Scholar 

  • Cheng FC, Kuo JS, Chia LG, Dryhurst G (1996) Elevated 5-S-cysteinyldopamine/homovanillic acid ratio and reduced homovanillic acid in cerebrospinal fluid: possible markers for and potential insights into the pathoetiology of Parkinson’s disease. J Neural Transm 103:433–446

    Article  PubMed  CAS  Google Scholar 

  • Fujishiro K, Hagihara M, Takahashi A, Nagatsu T (1990) Concentrations of neopterin and biopterin in the cerebrospinal fluid of patients with Parkinson’s disease. Biochem Med Metab Biol 44:97–100

    Article  PubMed  CAS  Google Scholar 

  • Fukushima T, Nixon JC (1980) Analysis of reduced forms of biopterin in biological tissues and fluids. Anal Biochem 102:176–188

    Article  PubMed  CAS  Google Scholar 

  • Funayama M, Hasegawa K, Kowa H, Saito M, Tsuji S, Obata F (2002) A new locus for Parkinson’s disease (PARK8) maps to chromosome 12p11.2–q13.1. Ann Neurol 51:296–301

    Article  PubMed  CAS  Google Scholar 

  • Furukawa Y, Nishi K, Kondo T, Tanabe K, Mizuno Y (1992) Significance of CSF total neopterin and biopterin in inflammatory neurological diseases. J Neurol Sci 111:65–72

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa K, Stoessl AJ, Yokoyama T, Kowa H, Wszolek ZK, Yagishita S (2009) Familial parkinsonism: study of original Sagamihara PARK8 (I2020T) kindred with variable clinicopathologic outcomes. Parkinsonism Relat Disord 15:300–306

    Article  PubMed  Google Scholar 

  • Kostic VS, Djuricic BM, Covickovic-Sternic N, Bumbasirevic L, Nikolic M, Mrsulja BB (1987) Depression and Parkinson’s disease: possible role of serotonergic mechanisms. J Neurol 234:94–96

    Article  PubMed  CAS  Google Scholar 

  • Levine RA, Miller LP, Lovenberg W (1981) Tetrahydrobiopterin in striatum: localization in dopamine nerve terminals and role in catecholamine synthesis. Science 214:919–921

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Liu W, Oo TF, Wang L, Tang Y, Jackson-Lewis V, Zhou C, Geghman K, Bogdanov M, Przedborski S, Beal MF, Burke RE, Li C (2009) Mutant LRRK2(R1441G) BAC transgenic mice recapitulate cardinal features of Parkinson’s disease. Nat Neurosci 12:826–828

    Article  PubMed  CAS  Google Scholar 

  • Li X, Patel JC, Wang J, Avshalumov MV, Nicholson C, Buxbaum JD, Elder GA, Rice ME, Yue Z (2010) Enhanced striatal dopamine transmission and motor performance with LRRK2 overexpression in mice is eliminated by familial Parkinson’s disease mutation G2019S. J Neurosci 30:1788–1797

    Article  PubMed  CAS  Google Scholar 

  • Lovenberg W, Levine RA, Robinson DS, Ebert M, Williams AC, Calne DB (1979) Hydroxylase cofactor activity in cerebrospinal fluid of normal subjects and patients with Parkinson’s disease. Science 204:624–626

    Article  PubMed  CAS  Google Scholar 

  • Melrose HL, Dachsel JC, Behrouz B, Lincoln SJ, Yue M, Hinkle KM, Kent CB, Korvatska E, Taylor JP, Witten L, Liang YQ, Beevers JE, Boules M, Dugger BN, Serna VA, Gaukhman A, Yu X, Castanedes-Casey M, Braithwaite AT, Ogholikhan S, Yu N, Bass D, Tyndall G, Schellenberg GD, Dickson DW, Janus C, Farrer MJ (2010) Impaired dopaminergic neurotransmission and microtubule-associated protein tau alterations in human LRRK2 transgenic mice. Neurobiol Dis 40:503–517

    Article  PubMed  CAS  Google Scholar 

  • Nandhagopal R, Mak E, Schulzer M, McKenzie J, McCormick S, Sossi V, Ruth TJ, Strongosky A, Farrer MJ, Wszolek ZK, Stoessl AJ (2008) Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study. Neurology 71:1790–1795

    Article  PubMed  CAS  Google Scholar 

  • Orimo S, Ozawa E, Nakade S, Sugimoto T, Mizusawa H (1999) (123)I-metaiodobenzylguanidine myocardial scintigraphy in Parkinson’s disease. J Neurol Neurosurg Psychiatry 67:189–194

    Article  PubMed  CAS  Google Scholar 

  • Orimo S, Amino T, Itoh Y, Takahashi A, Kojo T, Uchihara T, Tsuchiya K, Mori F, Wakabayashi K, Takahashi H (2005) Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease. Acta Neuropathol 109:583–588

    Article  PubMed  Google Scholar 

  • Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, Lopez de Munain A, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron 44:595–600

    Article  PubMed  CAS  Google Scholar 

  • Tong Y, Pisani A, Martella G, Karouani M, Yamaguchi H, Pothos EN, Shen J (2009) R1441C mutation in LRRK2 impairs dopaminergic neurotransmission in mice. Proc Natl Acad Sci USA 106:14622–14627

    Article  PubMed  CAS  Google Scholar 

  • Wszolek ZK, Pfeiffer RF, Tsuboi Y, Uitti RJ, McComb RD, Stoessl AJ, Strongosky AJ, Zimprich A, Muller-Myhsok B, Farrer MJ, Gasser T, Calne DB, Dickson DW (2004) Autosomal dominant parkinsonism associated with variable synuclein and tau pathology. Neurology 62:1619–1622

    PubMed  CAS  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, Carbajal IC, 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

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Ms. Aya Kumon for data analysis in Table 1. This study was supported by Health and Labor Sciences Research Grants for Research on Intractable Disease from the Ministry of Health, Labor and Welfare of Japan; by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health, Labor and Welfare of Japan; by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science; and by a Grant-in-Aid for JSPS Fellows (No. 20009634) from the Japan Society for the Promotion of Science. Shoko Koshiba is a JSPS research fellow.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biomolecular Engineering, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B7 Nagatsuta, Midori-ku, Yokohama, 226-8501, Japan

    Shoko Koshiba

  2. Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259-B7 Nagatsuta, Midori-ku, Yokohama, 226-8501, Japan

    Hirofumi Tokuoka & Hiroshi Ichinose

  3. Division of Neurology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara, 252-0392, Japan

    Teruo Yokoyama, Emiko Horiuchi & Kazuko Hasegawa

Authors
  1. Shoko Koshiba
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  2. Hirofumi Tokuoka
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  3. Teruo Yokoyama
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  4. Emiko Horiuchi
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  5. Hiroshi Ichinose
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  6. Kazuko Hasegawa
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Correspondence to Hiroshi Ichinose.

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Koshiba, S., Tokuoka, H., Yokoyama, T. et al. Biopterin levels in the cerebrospinal fluid of patients with PARK8 (I2020T). J Neural Transm 118, 899–903 (2011). https://doi.org/10.1007/s00702-011-0587-8

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  • DOI: https://doi.org/10.1007/s00702-011-0587-8

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