Pathophysiology: biochemistry of Parkinson's disease

Daniela Berg; Olaf Riess; Peter Riederer

doi:10.1017/CBO9780511544873.042

41 - Pathophysiology: biochemistry of Parkinson's disease

from Part VII - Parkinson's and related movement disorders

Published online by Cambridge University Press: 04 August 2010

Anthony E. Lang and

Olaf Riess and

M. Flint Beal: Affiliation:
Cornell University, New York
Anthony E. Lang: Affiliation:
University of Toronto
Albert C. Ludolph: Affiliation:
Universität Ulm, Germany
Daniela Berg: Affiliation:
Hertie Institute for Clinical Brain Research, Institute for Medical Genetics, Tübingen, Germany
Olaf Riess: Affiliation:
Institute for Medical Genetics, Tübingen, Germany
Peter Riederer: Affiliation:
Clinic and Policlinic of Psychiatry and Psychotherapy, University of Wurzburg, Germany

Book contents

Get access

Summary

Although the primary pathology and key defects of neurotransmission leading to the clinical picture of Parkinson's disease (PD) are known, initiation and nature of the neurodegenerative process are still obscure. However, it is becoming increasingly evident that the underlying pathophysiology is complex and in most cases probably multifactorial, differing among the individuals affected.

Only a very small percentage of Parkinsonian cases are caused by monogenic alterations (see Chapter 40). However, since the first description of a family in which 79 of 194 members suffered from PD (Mjörnes, 1949), it has become evident that the risk of developing the clinical picture of PD is three to four times higher in individuals with relatives with PD compared to those with a negative family history. Functional neuroimaging proved to be especially valuable for the detection of affected siblings: for monozygotic twins a concordance of 75% for PD or at least a subclinical dopaminergic deficit was detected by PET-studies, the rate for dizygotic was 22% (Piccini et al., 1999). These and other findings provide strong evidence of a genetic contribution to idiopathic PD (Gasser et al., 1998, 2001). However, only about 25% of PD patients report a relative affected by the same disease. Therefore, other factors are necessary to explain the selectivity and susceptibility of the disease on the basis of a genetic predisposition. Biochemical and histological investigations of the past decades have illuminated some of these factors.

Type: Chapter
Information: Neurodegenerative Diseases
Neurobiology, Pathogenesis and Therapeutics
, pp. 598 - 611

DOI: https://doi.org/10.1017/CBO9780511544873.042 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alam, Z. I., Jenner, A., Daniel, S. E.et al. (1997). Oxidative DNA damage in the parkinsonian brain: a selective increase in 8-hydroxyguanine in substantia nigra?J. Neurochem., 69, 1196–203CrossRef Google Scholar PubMed

Ambani, L. M., Woert, M. H. & Murphy, S. (1975). Brain peroxidase and catalase in Parkinson's disease. Arch. Neurol., 32, 114–18CrossRef Google Scholar

Anglade, P., Vyas, S., Hirsch, E. C.et al. (1997). Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol. Histopathol., 12, 25–31Google Scholar PubMed

Antunes, F., Han, D., Rettori, D. & Cadenas, E. (2002). Mitochondrial damage by nitric oxide potentiated by dopamine in PC12 cells. Biochim. Biophys. Act., 1556, 233–8CrossRef Google Scholar PubMed

Barbeau, A., Roy, M., Cloutier, T., Plasse, L. & Paris, S. (1987). Environmental and genetic factors in the etiology of Parkinson's disease. Adv. Neurol., 45, 299–306Google Scholar PubMed

Beal, M. F., Hyman, B. T. & Koroshetz, W. (1993). Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases. Trends Neurosci., 16, 125–31CrossRef Google Scholar PubMed

Beck, K. D., Knusel, B. & Hefti, F. (1993). The nature of the trophic action of brain-derived neurotrophic factor, des(T-3)-insulin-like growth factor, and basic fibroblast growth factor on mesencepahlic dopaminergic neurons developing in culture. Neuroscience, 52, 855–66CrossRef Google Scholar

Becker, G., Seufert, J., Bogdahn, U., Reichmann, H. & Reiners, K. (1995). Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography. Neurology, 45, 182–4CrossRef Google Scholar PubMed

Beckmann, J. S. (1996). Oxidative damage and tyrosine nitration from peroxynitrite. Chem. Res. Toxicol., 9, 836–44CrossRef Google Scholar

Beckmann, J. S., Beckmann, T. W., Chen, J., Marshall, P. A. & Freeman, P. A. (1990). Apparent hydroxyl radical production by peroxynitrite: implications for endothilial injury from nitric oxide and superoxide. Proc. Natl Acad. Sci., USA, 87, 1620–4CrossRef Google Scholar

Ben-Shachar, D., Riederer, P . & Youdim, M. B. (1991). Iron–melanin interaction and lipid peroxidation: implications for Parkinson's disease. J. Neurochem., 57, 1609–14CrossRef Google Scholar PubMed

Ben-Shachar, D., Zuk, R. & Glinka, Y. (1995). Dopamine neurotoxicity: inhibition of mitochondrial respiration. J. Neurochem., 64, 718–23CrossRef Google Scholar PubMed

Berg, D., Becker, G., Zeiler, B.et al. (1999a). Vulnerability of the nigrostriatal system as detected by transcranial ultrasound. Neurology, 53, 1026–31CrossRef Google Scholar

Berg, D., Grote, C., Rausch, W.-D., et al. (1999b). Iron accumulation of the substantia nigra in rats visualized by ultrasound. Ultrasound Med. Biol., 25, 901–4CrossRef Google Scholar

Berg, D., Gerlach, M ., Youdim, M. B. H.et al. (2001). Brain iron pathways and their relevance to Parkinson's disease. J. Neurochem., 79, 225–36CrossRef Google Scholar PubMed

Berg, D., Roggendorf, W., Schröder, U.et al. (2002). Echogenicity of the substantia nigra – association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch. Neurol., 59, 999–1005CrossRef Google Scholar PubMed

Berg, D., Riess, O. & Bornemann, A. (2003a). Specification of 14–3–3 proteins in Lewy bodies. Ann. Neurol., 54, 135CrossRef Google Scholar

Berg, D., Holzmann, C. & Riess, O. (2003b). 14–3–3 proteins in the nervous system. Nat. Rev. Neurosci., 4, 1–11CrossRef Google Scholar

Betarbet, R., Sherer, T. B., MacKenzie, G., Garcia-Osuna, M., Panov, A. V. & Greenamyre, J. Z. (2000). Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci., 3, 1301–6CrossRef Google Scholar PubMed

Bharat, S., Hsu, M., Kaur, D., Rajagopalan, S. & Andersen, J. K. (2002). Glutathione, iron and Parkinson's disease. Biochem. Pharmacol., 64, 1037–48CrossRef Google Scholar

Blum-Degen, D., Müller, T., Kuhn, W.et al. (1995). Interleukin-1-beta and interleukin 6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients. Neurosci. Lett., 202, 17–20CrossRef Google Scholar PubMed

Boka, G., Anglade, P., Wallach, D., Javoy-Agid, F., Agdi, Y. & Hirsch, E. C. (1994). Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease. Neurosci. Lett., 172, 151–4CrossRef Google Scholar PubMed

Borie, C., Gasparini, F., Verpillat, P.et al. (2002). Association study between iron-related genes polymorphisms and Parkinson's disease. J. Neurol., 249, 801–4CrossRef Google Scholar PubMed

Bostantjopoulou, S., Kyriazis, G., Katsarou, Z., Kiosseoglou, G., Kazis, A. & Mentenopouplos, G. (1997). Superoxide dismutase activity in early and advanced Parkinson's disease. Funct. Neurol., 12, 63–8Google Scholar PubMed

Bredt, D. S. (1999). Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic. Res., 31, 577–96CrossRef Google Scholar PubMed

Bringmann, G., Feineis, D., Grote, C. et al. (1998). Highly halogenated tetrahydro-β-carbolines as a new class of dopaminergic neurotoxins. In Pharmacology of Endogenous Neurotoxins. A Handbook, ed. A. Moser, pp. 151–69. Boston: BirkhäuserCrossRef

Burke, R. E. & Kholodilov, N. G. (1998). Programmed cell death: does it play a role in Parkinson's disease?Ann. Neurol., 44, S126–33CrossRef Google Scholar PubMed

Castellani, R. J., Siedlak, S. L., Perry, S. & Smith, M. A. (2000). Sequestration of iron by Lewy bodies in Parkinson's disease. Acta Neuropathol., 100, 111–14CrossRef Google Scholar PubMed

Chan-Palay, V., Zetsche, T. & Hochli, M. (1991). Parvalbumin neurons in the hippocampus in senile dementia of the Alzheimer type, Parkinson's disease and multi-infarct dementia. Dementia, 2, 297–313Google Scholar

Chiba-Falek, O. & Nussbaum, R. L. (2001). Effect of allelic variation at the NACP-Rep1 repeat upstream of the α-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system. Hum. Mol. Genet., 10, 3101–9CrossRef Google Scholar

Cleeter, M. W. J., Cooper, J. M., Darley Usmar, V. M., Moncada, S. & Schapira, A. H. V. (1994). Reversible inhibition of cytochrome c oxidase, the terminal enyzme of the mitochondrial respiratory chain, by nitric oxide: implications for neurodegenerative disorders. Acta Biochem. Biophys., 288, 481–7Google Scholar

Czlonkowska, A., Kurkowska-Jastrzebska, I., Czlonkowski, A., Peter, D. & Stefano, G. B. (2002). Immune processes in the pathogenesis of Parkinson's disease – a potential role for microglia and nitric oxide. Med. Sci. Monit., 8, 165–77Google Scholar PubMed

D'Amato, R. J., Lipman, Z. P. & Snyder, S. H. (1986). Selectivity of the Parkinson neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin. Science, 231, 987–9CrossRef Google Scholar PubMed

Damier, P., Hirsch, E. C., Zhang, P., Agid, Y. & Javoy-Agid, F. (1993). Glutathione peroxidase, glial cells and Parkinson's disease. Neuroscience, 52, 1–6CrossRef Google Scholar PubMed

Damier, P., Kastner, A., Agid, Y. & Hirsch, E. C. (1996). Does monoamine oxidase type B play a role in dopaminergic nerve cell death in Parkinson's disease?Neurology, 46, 1262–9CrossRef Google Scholar PubMed

David, G. C., Williams, A. C., Markey, S. P.et al. (1979). Chronic Parkinsonism secondary to intravenous injection of meperidine analogues. Psychiat. Res., 1, 249 – (PF Sz)Google Scholar

Desagher, S., Glowinski, J. & Premont, J. (1997). Pyruvate protects neurons against hydrogen peroxide-induced toxicity. J. Neurosci., 17, 9060–7CrossRef Google Scholar PubMed

Dexter, D. T., Cater, C. J., Wells, F. R.et al. (1989). Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J. Neurochem., 52, 381–9CrossRef Google Scholar PubMed

Dexter, D. T., Sian, J., Jenner, P. & Marsden, C. D. (1993). Implications of alterations in trace element levels in brain in Parkinson's disease and other neurological disorders affecting the basal ganglia. Adv. Neurol., 60, 273–81Google Scholar PubMed

Double, K. L., Riederer, P. & Gerlach, M. (1999). Significance of neuromelanin for neurodegeneration in Parkinson's disease. Drug News Perspect., 12, 333–40Google Scholar

Double, K. L., Gerlach, M., Youdim, M. B. H. & Riederer, P. (2000). Impaired iron homeostasis in Parkinson's disease. J. Neural Transm., 60, 37–58Google Scholar

Duvoisin, R. C., Zahr, M. D., Schweitzer, M. D.et al. (1963). Parkinsonism before and since the epidemic of encephalitis lethargica. Arch. Neurol., 9, 232–6CrossRef Google Scholar PubMed

Fahn, S. (1999). Parkinson disease, the effect of levodopa, and the ELLDOPA trial. Earlier vs later L-dopa. Arch. Neurol., 56, 529–35CrossRef Google Scholar PubMed

Farrer, M., Maraganore, D. M., Lockhart, P.et al. (2001). α-synuclein gene haplotypes are associated with Parkinson's disease. Hum. Mol. Genet., 10, 1847–51CrossRef Google Scholar PubMed

Ferrarese, C., Tremolizzo, L., Rigoldi, M., Sala, G. & Begni, B. (2001). Decreased platelet glutamate uptake and genetic risk factors in patients with Parkinson's disease. Neurol. Sci., 22, 65–6CrossRef Google Scholar PubMed

Foley, P. & Riederer, P. (1999). Pathogenesis and preclinical course of Parkinson's disease. J. Neural. Transm., 56, S31–74CrossRef Google Scholar PubMed

Friquet, B. & Szweda, L. I. (1997). Inhibition of the multicatalytic proteinase (proteasome) by the 4-hydroxy-2-nonenal cross linked protein. FEBS Lett., 405, 21–5CrossRef Google Scholar

Galvin, J. F., Lee, V. M. Y., Schmidt, L. et al. (1999). Pathology of the Lewy body. In Advances in Neurology, Vol 80, Parkinson's Disease, ed. G. Stern, pp. 313–24. Philadelphia: Lippincott Williams & Wilkins

Gamboa, E. T., Wolf, A., Yahr, M. D.et al. (1974). Influenza virus antigen in postencephalic parkinsonism brain. Arch. Neurol., 31, 228–32CrossRef Google Scholar

Gao, H. M., Jiang, J., Wilson, B., Zhang, W., Hong, J. S. & Liu, B. (2002). Microglia activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease. J. Neurochem., 81, 1285–97CrossRef Google Scholar PubMed

Gash, D. M., Zhang, Z., Ovadia, A.et al. (1996). Functional recovery in parkinsonian monkeys treated with GDNF. Nature, 380, 252–5CrossRef Google Scholar PubMed

Gasser, T. (1998). Genetics of Parkinson's disease. Ann. Neurol., 44, S53–7CrossRef Google Scholar PubMed

Gasser, T. (2001). Molecular genetics of Parkinson's disease. In Advances in Neurology, Vol 86, Parkinson's Disease, ed. D. Calne & S. Calne, pp. 23–32. Philadelphia: Lippincott Williams & Wilkins

Gerlach, M., Ben-Shachar, D., Riederer, P.et al. (1994). Altered brain metabolism of iron as a cause of neurodegenerative diseases. J. Neurochem., 63, 793–807CrossRef Google Scholar PubMed

Gerlach, M., Riederer, P. & Youdim, M. B. H. (1996). Molecular mechanisms for neurodegeneration: synergism between reactive oxygen species, calcium and excitotoxic amino acids. In Advances in Neurology, Vol 69, Parkinson's Disease., ed. L. Battistin, G. Scarlato, T. Caraceni & S. Ruggieri, pp. 177–94. Philadelphia: Lippincott-Raven

Gerlach, M., Reichmann, H. & Riederer, P. (2001). Die Parkinsonkrankheit, Grundlagen, Klinik, Therapie. Wien, New York: Springer

Giasson, B. I., Duda, J. E., Murray, I. V.et al. (2000). Oxidative damage linked to neurodegeneration by selective alpha-synuclein nitration in synucleinopathy lesions. Science, 3, 985–9CrossRef Google Scholar

Glass, J. (1983). Untersuchung zur Bedeutung chemischer Noxen in der Ätiologie des Parkinson Syndroms. In Pathophysiologie, Klinik und Therapie des Parkinsonismus, pp. 103–7. Basel: Roches

Goedert, M., Spillantini, M. G. & Davies, S. W. (1998). Filamentous nerve cell inclusions in neurodegenerative diseases. Curr. Opin. Neurobiol., 8, 619–32CrossRef Google Scholar PubMed

Golts, N., Snyder, H., Frasier, M., Theisler, C., Choi, P. & Wolozin, B. (2002). Magnesium inhibits spontaneous and iron-induced aggregation of alpha-synuclein. J. Biol. Chem., 277, 16116–23CrossRef Google Scholar PubMed

Good, P., Olanow, C. & Perl, D. (1992). Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminium in Parkinson's disease: a LAMMA study. Brain, 593, 343–6CrossRef Google Scholar PubMed

Götz, M. E., Künig, G., Riederer, P. & Youdim, M. B. H. (1994). Oxidative stress. Free radical production in neural degeneration. Pharmac. Ther., 63, 37–122CrossRef Google Scholar PubMed

Grisham, M. B., Jourd'Heul, D. & Wink, D. A. (1999). Nitric oxide I. Physiological chemistry of nitric oxide and its metabolites: implications in inflammation. Am. J. Physiol., 276, 315–21Google Scholar PubMed

Grune, T., Reinheckel, T., Joshi, M. & Davies, K. J. A. (1995). Proteolysis in cultured liver epithelial cells during oxidative stress. Role of multicatalytic proteinase complex proteasome. J. Biol. Chem., 270, 2344–51CrossRef Google Scholar PubMed

Gu, M., Cooper, J. M., Taanman, J. W. & Schapira, A. H. V. (1998). Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease. Ann. Neurol., 44, 177–86CrossRef Google Scholar PubMed

Gu, G., Reyes, P. E., Golden, G. T.et al. (2002). Mitochondrial DNA deletions/rearrangements in Parkinson disease and related neurodegenerative disorders. J. Neuropathol. Exp. Neurol., 61, 634–9CrossRef Google Scholar PubMed

Hallgren, B. & Sourander, P. (1958). The effect of age on non-haem iron in the human brain. J. Neurochem., 3, 41–51CrossRef Google Scholar

Hartmann, A., Hunot, S., Michel, P. P., Muriel, M. P. & Vyas, S. (2002). Caspase-3 activation: a vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proc. Natl Acad. Sci., USA, 97, 2875–80CrossRef Google Scholar

Hashimoto, M., Hsu, L. J., Sisk, A . et al. (1998). Human recombinant NACP/alpha-synuclein is aggregated and fibrillated in vitro: relevance for Lewy body disease. Brain. Res., 799, 301–6CrossRef Google Scholar PubMed

Hashimoto, M., Hsu, L. J., Xia, Y.et al. (1999). Oxidative stress induces amyloid-like aggregate formation of NACP/α-synuclein in vitro. NeuroReport, 10, 717–21CrossRef Google Scholar PubMed

Hashimoto, M., Hsu, L. J., Rockenstein, E., Takenouchi, T., Mallory, M. & Masliah, E. (2002). Alpha-synuclein protects against oxidative stress via inactivation of the c-Jun N-terminal kinase stress-signaling pathway in neuronal cells. J. Biol. Chem., 277, 11465–72CrossRef Google Scholar PubMed

Hattori, N., Tanaka, M., Ozawa, T. & Mizuno, Y. (1991). Immunohistochemical studies on complexes I, II, III and IV of mitochondria in Parkinson's disease. Ann. Neurol., 30, 563–71CrossRef Google Scholar PubMed

He, Y., Thong, P. S., Lee, T.et al. (1996). Increased iron in the substantia nigra of 6-OHDA induced parkinsonian rats: a nuclear microscopy study. Brain. Res., 735, 149–53CrossRef Google Scholar PubMed

Hirsch, E. C. (2000). Glial cells and Parkinson's disease. J. Neurol., 247 (II) 58–62CrossRef Google Scholar PubMed

Hirsch, E. C., Graybiel, A. M. & Agid, Y. A. (1988). Melanid dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease. Nature, 334, 345–8CrossRef Google Scholar

Hirsch, E. C., Mouatt, A., Thomasser, M., Javoy-Agid, F., Agid, Y. & Graybiel, A. M. (1992). Expression of calbindin D28K-like immunoreactivity in catecholaminergic cell groups in the human midbrain. Normal distribution and distribution in Parkinson's disease. Neurodegeneration, 1, 83–93Google Scholar

Holzmann, C., Krüger, R., Saecker, A. M.et al. (2003). Polymorphisms of the α-synuclein promoter: expression analyses and association studies in Parkinson's disease. J. Neural. Transm., 110, 67–76Google Scholar PubMed

Hunot, S., Dugas, N., Faucheux, B.et al. (1999). Fc epsilon-RII/CD23 is expressed in Parkinson's disease and induces, in vitro, production of nitric oxide and tumor necrosis factor-alpha in glial cells. J. Neurosci., 19, 3440–7CrossRef Google Scholar PubMed

Ichimura, T., Isobe, T., Okuyama, T., Yamauchi, T. & Fujisawa, H. (1987). Brain 14–3–3 protein is an activator protein that activates tryptophan 5-monooxygenase and tyrosine-3-monooxygenase in the presence of Ca2+-, calmodulin-dependent protein kinase II. FEBS Lett., 219, 79–82CrossRef Google Scholar PubMed

Iravani, M. M., Kashefi, K., Mander, P., Rose, S. & Jenner, P. (2002). Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration. Neuroscience, 110, 49–58CrossRef Google Scholar PubMed

Isgreen, W. P., Chutorian, A. M. & Fahn, S. (1976). Sequential parkinsonism and chorea following ‘mild’ influenza. Trans. Am. Neurol. Assoc., 101, 56–9Google Scholar

Itoh, K., Weis, S., Mehraein, P. & Muller-Hocker, J. (1997). Defects of cytochrome c oxidase in the substantia nigra of Parkinson's disease: an immunohistochemical and morphometric study. Mov. Disord., 12, 9–16CrossRef Google Scholar PubMed

Jacobson, M. D., Weil, M. & Raff, M. C. (1997). Programmed cell death in animal development. Cell, 88, 347–54CrossRef Google Scholar PubMed

Janetzky, B., Hauck, S., Youdim, M. B.et al. (1994). Unaltered aconitase activity, but decreased complex I activity in substantia nigra pars compacta of patients with Parkinson's disease. Neurosci. Lett., 169, 126–8CrossRef Google Scholar PubMed

Jangen-Hodge, J., Obin, M. S., Gong, X.et al. (1997). Regulation of ubiquitin-conjugating enzymes by glutathione following oxidative stress. J. Biol. Chem., 272, 28218–26CrossRef Google Scholar

Jellinger, K. A. (2000). Cell death mechanisms in Parkinson's disease. J. Neural Transm., 107, 1–29CrossRef Google Scholar PubMed

Jellinger, K., Kienzel, E., Rumpelmair, G.et al. (1992). Iron–melanin complex in substantia nigra of Parkinsonian brains: an X-ray microanalysis. J. Neurochem., 59, 1168–71CrossRef Google Scholar PubMed

Jenner, P. (2001). Parkinson's disease, pesticides and mitochondrial dysfunction. Trends Neurosci., 24, 245–6CrossRef Google Scholar PubMed

Jenner, P. & Olanow, C. W. (1998). Understanding cell death in Parkinson's disease. Ann. Neurol., 44, S72–84CrossRef Google Scholar PubMed

Junn, E. & Mouradian, M. M. (2002). Human alpha-synuclein over-expression increases intracellular reactive oxygen species and susceptibility to dopamine. Neurosci. Lett., 320, 146–50CrossRef Google Scholar

Kawamato, Y., Akiguchi, S., Nakamura, Y., Honjyo, H., Shibasaki, H. & Budka, H. (2002). 14–3–3 proteins in Lewy bodies in Parkinson disease and diffuse Lewy body disease brain. J. Neuropathol. Exp. Neurol., 61, 245–53CrossRef Google Scholar

Kish, S. J., Morito, C. H. & Hornykiewics, (1985). Glutathione peroxidase activity in Parkinson's disease brain. Neurosci. Lett., 58, 343–6CrossRef Google Scholar PubMed

Kitazawa, M., Anantharam, V. & Kanthasamy, A. G. (2001). Dieldrin-induced oxidative stress and neurochemical changes contribute to apoptotic cell death in dopaminergic cells. Free Radic. Biol. Med., 31, 1473–85CrossRef Google Scholar PubMed

Koutsilieri, E., Scheller, C., Tribl, F. & Riederer, P. (2002). Degeneration of neuronal cells due to oxidative stress – microglial contribution. Parkinsonism Relat. Disord., 8, 401–6CrossRef Google Scholar PubMed

Kramer, B. C., Yabut, J. A., Cheong, J.et al. (2002). Lipopolysaccharide prevents cell death caused by glutathione depletion: possible mechanism of protection. Neuroscience, 114, 361–72CrossRef Google Scholar

Krüger, R., Vieira-Saecker, A. M. M., Kuhn, W.et al. (1999). Ann Neurol., 45, 611–173.0.CO;2-X>CrossRef

Krüger, R., Eberhardt, O., Riess, O. & Schulz, J. B. (2002). Parkinson's disease: one biochemical pathway to fit all genes?Trends Mol. Med., 8, 236–40CrossRef Google Scholar PubMed

Lan, J. & Jiang, D. H. (1997). Excessive iron accumulation in the brain: a possible potential risk of neurodegeneration in Parkinson's disease. J. Neural. Transm., 104, 649–60CrossRef Google Scholar PubMed

Landfield, P. W., Applegate, M. D., Schwitzer-Osborne, S. E. & Naylor, C. E. (1991). Phosphate/calcium alterations in the first stages of Alzheimer's disease: implications for etiology and pathogenesis. J. Neurol. Sci., 106, 221–9CrossRef Google Scholar PubMed

Langston, J. W., Ballard, P., Tetrud, J. W. & Irwin, I. (1983). Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science, 219, 989–90CrossRef Google Scholar PubMed

LeCouteur, D. G., Muller, M., Yang, M. C., Mellick, G. D. & McLean, A. J. (2002). Age–environment and gene–environment interactions in the pathogenesis of Parkinson's disease. Rev. Environm. Hlth., 17, 51–64Google Scholar

Lin, L. F., Doherty, D. H., Lile, J. D., Bektesh, S. & Collins, F. (1993). GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science, 260, 1130–2CrossRef Google Scholar PubMed

Liu, B., Gao, H., Wang, J., Jeohn, G., Cooper, C. & Hong, J. (2002). Role of nitric oxide in inflammation-mediated neurodegeneration. Ann. NY Acad. Sci. 962, 318–31CrossRef Google Scholar PubMed

Liu, Y., Fiskum, G. & Schubert, D. (2002). Generation of reactive oxygen species by the mitochondrial electron transport chain. J. Neurochem., 80, 780–7CrossRef Google Scholar PubMed

Lopiano, L., Chiesa, M., Digilio, G.et al. (2000). Q-band EPR investigations of neuromelanin in control and Parkinson's disease patients. Biochim. Biophys., 17, 306–12CrossRef Google Scholar

Lotharius, J. & Brundin, P. (2002). Impaired dopamine storage resulting from alpha-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum. Mol. Genet., 11, 2395–405CrossRef Google Scholar PubMed

Lowe, J., Lennox, G. & Leigh, P. N. (1997). Disorders of movement and system degenerations. In Greenfield's Neuropathology, 6th edn. ed. D. Graham & P. L. Lantos, pp. 280–366. London: Edward Arnold

Martilla, R. J., Lorentz, H. & Rinne, U. K. (1988). Oxygen toxicity protecting enzymes in Parkinson's disease: increase of superoxide-dismutase-like activity in the substantia nigra and basal nucleus. J. Neurol. Sci., 86, 321–31CrossRef Google Scholar

Maruyama, W. & Naoi, M. (2002). Cell death in Parkinson's disease. J. Neurol., 249 (11), 6–10CrossRef Google Scholar PubMed

McNaught, K. S. P. & Jenner, P. (2000). Extracellular accumulation of nitric oxide, hydrogen peroxide and glutamate in astrocytic cultures following glutathione depletion, complex I inhibition and/or lipopolysaccharide-induced activation. Biochem. Pharmacol., 60, 979–88CrossRef Google Scholar PubMed

Migliore, L., Petrozzi, L., Lucetti, C.et al. (2002). Oxidative damage and cytogenetic analysis in leukocytes of Parkinson's disease patients. Neurology, 58, 1809–15CrossRef Google Scholar PubMed

Minghetti, L. & Levi, G. (1998). Microglia as effector cells in brain damage and repair: focus on prostanoids and nitric oxide. Prog. Neurobiol., 54, 99–125CrossRef Google Scholar PubMed

Mizuno, Y., Ohta, S., Tanaka, M.et al. (1989). Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem. Biophys. Res. Commun., 163, 1450–5CrossRef Google Scholar PubMed

Mjörnes, H. (1949). Paralysis agitans: a clinical and genetic study. Acta Psychiatr. Neurol., 54, 1–95Google Scholar

Mochizuki, H., Imai, H., Endo, K.et al. (1994). Iron accumulation in the substantia nigra of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. Neurosci. Lett., 168, 251–3CrossRef Google Scholar PubMed

Mochizuki, H., Goto, K., Mori, H.et al. (1996). Histochemical detection of apoptosis in Parkinson's disease. J. Neurol. Sci., 137, 120–3CrossRef Google Scholar PubMed

Mogi, M., Harada, M., Kondo, T.et al. (1994). Interleukin-1 beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci. Lett., 180, 147–50CrossRef Google Scholar PubMed

Mogi, M., Harada, M., Narabayashi, H., Inagaki, H., Minami, M. & Nagatsu, T. (1996). Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease. Neurosci. Lett., 211, 13–16CrossRef Google Scholar PubMed

Muchowski, P. J. (2002). Protein misfolding, amyloid formation, and neurodegeneration: a critical role for molecular chaperones?Neuron, 35, 9–12CrossRef Google Scholar PubMed

Münch, G., Lüth, H. J., Wong, A.et al. (2000). Crosslinking of α-synuclein by advanced glycation endproducts – an early pathophysiological step in Lewy body formation. J. Clin. Neuroanatom., 20, 253–7CrossRef Google Scholar PubMed

Münch, G., Gerlach, M., Sian, J., Wong, A. & Riederer, P. (1998). Advanced glycation end products in neurodegeneration: more than early markers of oxidative stress?Ann. Neurol., 44 (Suppl 1), S85–8CrossRef Google Scholar PubMed

Muslin, A. J. & Xing, H. (2000). 14–3–3 proteins: regulation of subcellular localization by molecular interference. Cell. Signallin., 12, 703–9CrossRef Google Scholar PubMed

Mytilineou, C., Kramer, B. C. & Yabut, J. A. (2002). Glutathione depletion and oxidative stress. Parkinsonism Relat Disord., 8, 385–7CrossRef Google Scholar PubMed

Nagatsu, T. (2002). Parkinson's disease: changes in apoptosis-related factors suggesting possible gene therapy. J. Neural Transm., 109, 731–45CrossRef Google Scholar PubMed

Nagatsu, T., Mogi, M., Ichinose, H., Togari, A. & Riederer, P. (1999). Cytokines in Parkinson's disease. NeuroSci. New., 2, 88–90Google Scholar

Naoi, M., Maruyama, W., Akao, Y., Zhang, J. & Parvez, H. (2000). Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopamine neurons. Toxicology, 153, 123–41CrossRef Google Scholar PubMed

Naoi, M., Maruyama, W., Akao, Y. & Yi, H. (2002). Mitochondria determine the survival and death in apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, and neuroprotection by propargylamines. J. Neural Transm., 109, 607–21CrossRef Google Scholar PubMed

Nielsen, M. S., Vorum, H., Lindersson, E. & Jensen, P. H. (2001). Ca2+ binding to alpha-synuclein regulates ligand binding and oligomerization. J. Biol. Chem., 276, 22680–4CrossRef Google Scholar PubMed

Osterova-Golts, N., Petrucelli, L., Hardz, J., Lee, J. M., Farer, M. & Wolozin, B. (2000). The A53T α-Synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci., 20, 6048–54CrossRef Google Scholar

Osterova, N., Petrucelli, L., Farrer, M.et al. (1999). α-synuclein shares physical and functional homology with 14–3–3 proteins. J. Neurosci., 19, 5782–91CrossRef Google Scholar

Paik, S., Shin, H., Lee, J., Chang, C. & Kim, J. (1999). Copper(II)-induced self oligomerization of α-synuclein. Biochem. J., 340, 821–8CrossRef Google Scholar PubMed

Parent, A. & Cicchetti, F. (1998). The current model of basal ganglia organisation under scrutiny. Mov. Disord., 13, 199–202CrossRef Google Scholar PubMed

Perry, T. L., Young, V. W., Ito, M., et al. (1984). Nigrostriatal dopaminergic neurons remain undamaged in rats given high doses of L-Dopa and carbidopa chronically. J. Neurochem., 43, 990–3CrossRef Google Scholar PubMed

Piccini, P., Burn, D. J., Ceravolo, R., Maraganore, D. & Brooks, D. J. (1999). The role of inheritance in sporadic Parkinson's disease: evidence from a longitudinal study of dopaminergic function in twins. Ann. Neurol., 45, 577–823.0.CO;2-O>CrossRef Google Scholar PubMed

Plaitakis, A. & Shashidharan, P. (2000). Glutamate transport and metabolism in dopaminergic neurons of substantia nigra: implications for the pathogenesis of Parkinson's disease. J. Neurol., 247, S25–35CrossRef Google Scholar PubMed

Pollanen, M. S., Dickson, D. W. & Bergeron, C. (1993). Pathology and biology of the Lewy Body. J. Neuropathol. Exp. Neurol., 52, 183–91CrossRef Google Scholar PubMed

Poskanzer, D. C. & Schwab, R. S. (1963). Cohort analysis of Parkinson's syndrome: evidence for a single etiology related to subclinical infection about 1920. J. Chron. Dis., 16, 961–73CrossRef Google Scholar PubMed

Power, J. H., Shannon, J. M., Blumbergs, P. C. & Gai, W. P. (2002). Nonselenium glutathione peroxidase in human brain: elevated levels in Parkinson's disease and dementia with Lewy bodies. Am. J. Pathol., 161, 885–94CrossRef Google Scholar PubMed

Rajput, A. H., Uitti, R. J., Stern, W. & Laverty, W. (1986). Early onset Parkinson's disease and childhood environment. Adv. Neurol., 45, 295–7Google Scholar

Rajput, A. H., Ryan, J., Uitti, W.et al. (1987). Geography, drinking water chemistry, pesticides and herbicides and the etiology of Parkinson's disease. Can. J. Neurol. Sci., 14, 414–18CrossRef Google Scholar PubMed

Reichmann, H. & Janetzky, B. (2000). Mitochondrial dysfunction – a pathogenetic factor in Parkinson's disease. J. Neurol., 247, S63–7CrossRef Google Scholar PubMed

Reichmann, H. & Riederer, P. (1989). Biochemical analyses of respiratory chain enzymes in different brain regions of patients with Parkinson's disease. BMFT Symposium ‘Morbus Parkinson und andere Basalganglienerkrankungen’, Bad Kissingen (Abstract S 44)

Reichmann, H., Lestienne, P., Jellinger, K. & Riederer, P. (1993). Parkinson's disease and the electron transport chain in post mortem brain. In Advances in Neurology, Vol 60, Parkinson's Disease: From Basic Research to Treatment, ed. H. Narabayashi, T. Nagatsu, N. Yanagisawa & Y. Mizuno, pp. 297–9. New York: Raven

Reif, D. W. & Simmons, R. D. (1990). Nitric oxide mediates iron release from ferritin. Arch. Biochem. Biophys., 283, 537–41CrossRef Google Scholar PubMed

Riederer, P. & Foley, P. (2002). Mini-review: multiple developmental forms of parkinsonism. The basis for further research as to the pathogenesis of parkinsonism. J. Neural Transm., 109, 1469–75CrossRef Google Scholar PubMed

Riederer, P. & Youdim, M. B. H. (eds.) (1993). Iron in Central Nervous System Disorders. Vienna: Springer

Riederer, P., Rausch, W. D., Schmidt, B.et al. (1988). Biochemical fundamentals of Parkinson's disease. Mt. Sinai J. Med., 55, 21–8Google Scholar PubMed

Riederer, P., Sofic, E., Rausch, W. D.et al. (1989). Transition metals, ferritin, glutathione and ascorbic acid in Parkinsonian brains. J. Neurochem., 52, 515–20CrossRef Google Scholar PubMed

Ross, B. M., Moszczynska, A., Ehrlich, J. & Kish, S. J. (1998). Low activity of key phospholipid catabolic and anabolic enzymes in human substantia nigra: possible implications for Parkinson's disease. Neuroscience, 83, 791–8CrossRef Google Scholar PubMed

Rubanyi, G. M., Ho, E. H., Cantor, E. H., Lumma, W. C. & Botelho, L. H. (1991). Cytoprotective function of nitric oxide: inactivation of superoxide radicals produced by human leukocytes. Biochem. Biophys. Res. Commun., 181, 1392–7CrossRef Google Scholar PubMed

Sanchez-Ramos, J. R., Hefti, F. & Weiner, W. J. (1987). Paraquat and Parkinson's disease. Neurology, 37, 728CrossRef Google Scholar PubMed

Sanchez-Ramos, J. R., Övervik, E. & Ames, B. N. (1994). A marker of oxyradical-mediated DNA damage (8-hydroxy-2′-deoxyguanosine) is increased in nigro-striatum of Parkinson's disease brain. Neurodegeneration, 3, 197–204Google Scholar

Scherman, D., Desnos, C., Darchen, F., Javoy-Agid, F. & Agid, Y. (1989). Striatal dopamine deficiency in Parkinson's disease: role of aging. Ann. Neurol., 26, 551–7CrossRef Google Scholar

Secchi, G. P., Angetti, V., Piredda, M.et al. (1992). Acute and persistent parkinsonism after use of diquat. Neurology, 42, 261–3CrossRef Google Scholar

Serra, J. A., Domiguez, R. O., Lustig, E. S.et al. (2001). Parkinson's disease is associated with oxidative stress: comparison of peripheral antioxidant profiles in living Parkinson's, Alzheimer's and vascular dementia patients. J. Neural Transm., 108, 1135–48CrossRef Google Scholar PubMed

Shaw, C. A. & Bains, J. S. (2002). Synergistic versus antagonistic actions of glutamate and glutathione: the role of excitotoxicity and oxidative stress in neuronal disease. Cell Mol. Biol., 48, 127–36Google Scholar PubMed

Sherer, T. B., Betarbet, R. & Greenamyre, J. T. (2001). The rotenone model of Parkinson's disease in vivo: selective striatal oxidative damage and caspase-3 activation in nigrostriatal neurons. Soc. Neurosci. Abstr., 27, 653–2Google Scholar

Sherer, T. B., Betarbet, R. & Greenamyre, J. T. (2002a). Environment, mitochondria, and Parkinson's disease. Neuroscientist, 8, 192–7Google Scholar

Sherer, T. B., Betarbet, R., Stout, A. K., Lund, S. & Baptista, M. (2002b). An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered α-synuclein metabolism and oxidative damage. J. Neurosci., 22, 7006–15CrossRef Google Scholar

Shima, T., Sarna, T., Swartz, H., Stroppolo, A., Gerbasi, R. & Zecca, L. (1997). Binding of iron to neuromelanin of human substantia nigra and synthetic neuromelanin: an electron paramagnetic resonance spectroscopy study. Free Radic. Biol. Med., 23, 110–19CrossRef Google Scholar

Sian, J., Dexter, D. T., Lees, A. J., Daniel, S., Jenner, P. & Marsden, C. D. (1994). Glutathione-related enzymes in brain in Parkinson's disease. Ann. Neurol., 36, 356–61CrossRef Google Scholar PubMed

Singleton, A., Farrer, M., Johnson, J.et al. (2003). Triplication of the normal α-synuclein gene is a cause of hereditary Parkinson's disease. Science, 302, 841CrossRef Google Scholar

Sofic, E., Riederer, P., Heinsen, H.et al. (1988). Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J. Neural. Transm., 74, 199–205CrossRef Google Scholar PubMed

Sofic, E., Lange, K. W., Jellinger, K. & Riederer, P. (1992). Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease. Neurosci. Lett., 142, 128–130CrossRef Google Scholar PubMed

Solbrig, M. V. (1993). Acute parkinsonism in suspected herpes simplex encephalitis. Mov. Disord., 8, 233–4CrossRef Google Scholar PubMed

Souza, J. M., Giasson, B. I., Chen, Q., Lee, V. M. & Ischiropoulos, H. (2000). Dityrosine cross-linking promotes formation of stable α-synuclein polymers. Implication of nitrative and oxidative stress in the pathogenesis of neurodegenerative synucleinopathies. J. Biol. Chem., 275, 18344–9CrossRef Google Scholar PubMed

Spencer, J. P. E., Jenner, A., Aruoma, O. I.et al. (1994). Intense oxidative DNA damage promoted by L-Dopa and its metabolites: implications for neurodegenerative disease(S?). FEBS Lett., 353, 246–50CrossRef Google Scholar

Spencer, P. S., Nunn, P. B., Hugon, J.et al. (1987). Guam amyotrophic lateral sclerosis-parkinsonism-dementia linked to a plant excitant neurotoxin. Science, 237, 517–22CrossRef Google Scholar PubMed

Starkov, A. A., Polster, B. M. & Fiskum, G. (2002). Regulation of hydrogen peroxide production by brain mitochondria by calcium and Bax. J. Neurochem., 83, 220–8CrossRef Google Scholar PubMed

Tanaka, M. (2002). Mitochondrial genotypes and cytochrome b variants associated with longevity or Parkinson's disease. J. Neurol., 249 (III), 1–8CrossRef Google Scholar PubMed

Tatton, N. A. (2000). Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease. Exp. Neurol., 166, 29–43CrossRef Google Scholar PubMed

Tatton, N. A., Mallean-Fraser, A., Tatton, W. G.et al. (1998). A fluorescent double labeling method to detect and confirm apoptotic nuclei in Parkinson's disease. Ann. Neurol., 44, S142–8CrossRef Google Scholar PubMed

Thompson, C. B. (1995). Apoptosis in the pathogenesis of disease. Science, 267, 1456–62CrossRef Google Scholar

Tompkins, M. M. & Hill, W. D. (1997). Contribution of somal Lewy bodies to neuronal death. Brain Res., 775, 24–9CrossRef Google Scholar PubMed

Trojanowski, J. Q. & Lee, V. M.-Y. (2001). Parkinson's disease and related neurodegenerative synucleinopathies linked to progressive accumulation of synuclein aggregates in brain. Parkinsonism Rel. Disord., 7, 247–51CrossRef Google Scholar

Tu, P. H., Robinson, K. A., Snoo, F.et al. (1997). Selective degeneration of Purkinje cells with Lewy body-like inclusions in aged NFHLACZ transgenic mice. J. Neurosci., 17, 1064–74CrossRef Google Scholar PubMed

Turmel, H., Hartmann, A., Parain, K. (2001). Caspase-3 activation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Mov. Disord., 16, 185–9CrossRef Google Scholar PubMed

Turnbull, S., Tabner, B. J., El-Agnaf, O. M. A., Moore, S., Davies, Y. & Allsop, D. (2001). α-synuclein implicated in Parkinson's disease catalyses the formation of hydrogen peroxide in vitro. Free Radic. Biol. Med., 30, 1163–70CrossRef Google Scholar PubMed

Tzivion, G., Shen, Y. H. & Zhu, J. (2001). 14–3–3 proteins; bringing new definitions to scaffolding. Oncogene, 20, 6331–8CrossRef Google Scholar PubMed

Ubl, A., Berg, D., Holzmann, C.et al. (2002). 14–3–3 protein is a component of Lewy bodies in Parkinson's disease – mutation analysis and association studies of 14–3–3 eta. Mol. Brain. Res., 108, 33–9CrossRef Google Scholar PubMed

Walinshaw, G. & Waters, C. M. (1995). Induction of apoptosis in catecholaminergic PC12 cells by L-Dopa: implications for the treatment of Parkinson's disease. J. Clin. Invest., 95, 2458–64CrossRef Google Scholar

Walters, J. H. (1960). Postencephalitic Parkinson syndrome after meningoencephalitis due to Coxsacki virus group B, type 2. N. Engl. J. Med., 263, 744–7CrossRef Google Scholar

Welch, K. & Yuan, J. (2002). Releasing the nerve cell killers. Nat. Med. 8, 564–5CrossRef Google Scholar PubMed

Wüllner, U., Kornhuber, J. & Weller, M. (1999). Cell death and apoptosis regulating proteins in Parkinson's disease – a cautionary note. Acta Neuropathol., 97, 408–12Google Scholar PubMed

Xu, J., Kao, S. Y., Lee, F. J. S., Song, W., Jin, L. W. & Yankner, B. A. (2002). Dopamine-dependent neurotoxicity of α-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat. Med., 8, 600–6CrossRef Google Scholar PubMed

Yamada, T., McGeer, P. L., Baimbridge, K. G. & McGeer, E. G.(1990). Relative sparing in Parkinson's disease of substantia nigra neurons containing calbindin D28K. Brain Res., 526, 303–7CrossRef Google Scholar PubMed

Yoshida, E., Mokuno, K., Aoki, S. I.et al. (1994). Cerebrospinal fluid levels of superoxide dismutase. Neurol. Sci., 124, 25–31CrossRef Google Scholar

Youdim, M. B., Ben-Shachar, D. & Riederer, P. (1994). The enigma of neuromelanin in Parkinson's disease substantia nigra. J. Neural Transm., 43, S113–22Google Scholar PubMed

Youdim, M. B., Grunblatt, E. & Mandel, S. (1999). The pivotal role of iron in NF-kappa B activation and nigrostriatal dopaminergic neurodegeneration. Prospects for neuroprotection in Parkinson's disease with iron chelators. Ann. NY Acad. Sci., 890, 7–25CrossRef Google Scholar PubMed

Zareba, M., Bober, A., Korytowski, W., Zecca, L. & Sarna, T. (1995). The effect of a synthetic neuromelanin on yield of free hydroxyl radicals generated in model systems. Biochim. Biophys. Acta., 1271, 343–8CrossRef Google Scholar PubMed

Zayed, J., Ducic, S., Campanella, G.et al. (1990). Facteurs environnementeaux dans la maladie de Parkinson. Can. J. Neurol. Sci., 17, 286–91CrossRef Google Scholar

Zecca, L. & Swartz, H. M. (1993). Total and paramagnetic metals in human substantia nigra and its neuromelanin. J. Neural Transm., 5, 203–13CrossRef Google Scholar PubMed

Zecca, L., Mecacci, O., Seraglia, R. & Parati, E. (1992). The chemical characterization of melanin contained in substantia nigra of human brain. Biochim. Biophys. Act., 1138, 6–10CrossRef Google Scholar PubMed

Zecca, L., Shima, T., Stroppolo, A.et al. (1996). Interaction of neuromelanin and iron in the substantia nigra and other areas of human brain. Neuroscience, 73, 407–15CrossRef Google Scholar PubMed

Zecca, L., Gallorini, M., Schünemann, V.et al. (2001). Iron, neuromelanin and ferritin in substantia nigra of normal subjects at different ages. Consequences for iron storage and neurodegenerative processes. J. Neurochem., 76, 1766–73CrossRef Google Scholar PubMed

Zecca, L.Fariello, R., Riederer, P., Sulzer, D., Gatti, A. & Tampellini, D. (2002). The absolute concentration of nigral dopamine, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson's disease. FEBS Lett., 510, 216–20CrossRef Google Scholar

Book contents

41 - Pathophysiology: biochemistry of Parkinson's disease

Summary

Access options

References

Save book to Kindle

Save book to Dropbox

Save book to Google Drive