Abstract
The understanding of oxidative damage in different neurodegenerative diseases could enhance therapeutic strategies. Our objective was to quantify lipoperoxidation and other oxidative products as well as the activity of antioxidant enzymes and cofactors in cerebrospinal fluid (CSF) samples. We recorded data from all new patients with a diagnosis of either one of the four most frequent neurodegenerative diseases: Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and lateral amyotrophic sclerosis (ALS). The sum of nitrites and nitrates as end products of nitric oxide (NO) were increased in the four degenerative diseases and fluorescent lipoperoxidation products in three (excepting ALS). A decreased Cu/Zn-dependent superoxide dismutase (SOD) activity characterized the four diseases. A significantly decreased ferroxidase activity was found in PD, HD and AD, agreeing with findings of iron deposition in these entities, while free copper was found to be increased in CSF and appeared to be a good biomarker of PD.
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References
Price DL (1999) New order from neurological disorders. Nature 399(suppl):A3–A5
Halliwell B (1992) Reactive oxygen species in the central nervous system. J Neurochem 59:1609–1623
Ischiropoulos H, Beckman JS (2003) Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J Clin Invest 111:163–169
Jenner P, Schapira AH, Marsden CD (1992) New insights into the cause of Parkinson’s disease. Neurology 42:2241–2250
Schon EA, Manfredi G (2003) Neuronal degeneration and mitochondrial dysfunction. J Clin Invest 111:303–312
Youdim MBH, Ben Shachar D, Yehuda S, Riederer P (1990) The role of iron in the Basal Ganglion. Adv Neurol 53:155–162
Dexter DT, Jenner P, Schapira AHV, Marsden CD (1992) Alterations in levels of iron, ferritin, and other trace metals in neurodegenerative diseases affecting the basal ganglia. Ann Neurol 32:S94–S100
Rios C, Alvarez-Vega R, Rojas P (1995) Depletion of copper and manganese in brain after MPTP treatment of mice. Pharmacol Toxicol 76:348–352
Alcaraz-Zubeldia M, Rojas P, Boll C, Rios C (2001) Neuroprotective effect of acute and chronic administration of copper (II) sulfate against MPP+ neurotoxicity in mice. Neurochem Res 26:59–64
Pall HS, Williams AC, Blake DR et al (1987) Raised cerebrospinal-fluid copper concentration in Parkinson’s disease. Lancet 2:238–241
Boll MC, Sotelo J, Otero E, Alcaraz-Zubeldia M, Rios C (1999) Reduced ferroxidase activity in the CSF from patients with Parkinson’s disease. Neurosci Lett 265:155–158
Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotid repeat that is unstable on Huntington’s disease chromosomes. Cell 72:971–983
McKhann G, Drachman D, Folstein M et al (1994) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services task force on Alzheimer’s disease. Neurology 34:939–944
Rothstein JD, Van Kammen M, Levey AI, Martin J, Kuncl JW (1995) Selective loss of glial glutamate transporter GTL1 in amyotrophic lateral sclerosis. Ann Neurol 38:73–84
Zoia C, Cogliati T, Tagliabue E et al (2004) Glutamate transporters in platelets: EAAT1 decrease in aging and in Alzheimer’s disease. Neurobiol Aging 25:149–157
Zecca L, Rosati M, Renella R et al (1998) Nitrite and nitrate levels in cerebrospinal fluid of normal subjects. J Neural Transm 105:627–633
Naidoo R, Knapp ML (1992) Studies of lipid peroxidation products in cerebrospinal fluid and serum in multiple sclerosis and other conditions. Clin Chem 38:2449–2454
Rosen DR, Siddique T, Patterson D et al (1993) Mutations in Cu/Zn superoxide dismutase are associated with familiar amyotrophic lateral sclerosis. Nature 362:59–62
Waggoner DJ, Bartnikas TB, Gitlin JD (1999) The role of copper in neurodegenerative diseases. Neurobiol Dis 6:221–230
Harris ZL, Takahashi Y, Miyajima H, Serizawa M, McGiliwray RTA, Gitlin JD (1995) Aceruloplasminemia: molecular characterization of this disorder of iron metabolism. Proc Natl Acad Sci USA 92:2539–2543
Alonso ME, Yescas P, Cisneros B et al (1997) Analysis of the (CAG)n repeat causing Huntington’s disease in a Mexican population. Clin Genet 51:225–230
Huntington Study Group (1996) Unified Huntington’s disease rating scale: reliability and consistency. Mov Disord 11:136–142
Folstein MF, Folstein SE, McHugh PR (1975) “Mini- mental state”: a practical method for grading the cognitive state of subjects for the clinician. J Psychiatr Res 12:189–198
Moroney JT, Bagiella E, Desmond DW et al (1997) Meta-analysis of the Hachinski Ischemic score in pathologically verified dementias. Neurology 49:1096–1105
Brooks BR (1994) El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis: subcommittee on motor neuron diseases/amyotrophic lateral sclerosis of the World Federation of Neurology research group on neuromuscular diseases and the El Escorial “clinical limits of amyotrophic lateral sclerosis” workshop contributors. J Neurol Sci 124(suppl):96–107
ALS CNTF Treatment Study Phase I-II Study Group (1996) The ALS functional rating scale: assessment of activities of daily living in patients with amyotrophic lateral sclerosis. Arch Neurol 53:141–147
Boll MC, Alcaraz-Zubeldia M, Montes S, Murillo-Bonilla LM, Rios C (2003) Raised nitrates level and low SOD activity in the CSF in sporadic ALS. Neurochem Res 28(5):699–703
Gutteridge JMC, Halliwell B (1990) The measurement and mechanism of lipid peroxidation in biological systems. TIBS 15:129–135
Estevez AG, Spear N, Manuel SM et al (1998) Role of endogenous nitric oxide and peroxynitrite formation in the survival and death of motor neurons in culture. Prog Brain Res 118:269–280
Brookes P, Levonen AL, Shiva S et al (2002) Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Rad Biol Med 33:755–764
Corona JC, Tovar-y-Romo LB, Tapia R (2007) Glutamate excitotoxicity and therapeutic targets for amyotrophic lateral sclerosis. Expert Opin Ther Targets 11:1415–1428
Hochstrasser H, Bauer P, Walter U et al (2004) Ceruloplasmin gene variations and substantia nigra hyperechogenicity in Parkinson disease. Neurology 63:1912–1917
Patel BN, Dunn RJ, Jeong SY et al (2002) Ceruloplasmin regulates iron levels in the CNS and prevents free radical injury. J Neurosci 2215:6578–6586
Bayer TA, Multhaup G (2005) Involvement of amyloid beta precursor protein (AbetaPP) modulated copper homeostasis in Alzheimer’s disease. J Alzheimers Dis 8:201–206
Brown DR (2001) Copper and prion disease. Brain Res Bull 55:165–173
Acknowledgments
The authors wish to thank all physicians and nurses involved in this study for their help and support, in particular Dr. Noffal from the clinical laboratory of the NINN. A doctoral grant No. 96086 from CONACyT also provided considerable support to this work.
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Boll, MC., Alcaraz-Zubeldia, M., Montes, S. et al. Free Copper, Ferroxidase and SOD1 Activities, Lipid Peroxidation and NO x Content in the CSF. A Different Marker Profile in Four Neurodegenerative Diseases. Neurochem Res 33, 1717–1723 (2008). https://doi.org/10.1007/s11064-008-9610-3
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DOI: https://doi.org/10.1007/s11064-008-9610-3