nach oben

NeuroMolecular Medicine

Erschienen in:

01.12.2008 | Review Paper

Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases

verfasst von: Peter J. Adhihetty, M. Flint Beal

Erschienen in: NeuroMolecular Medicine | Ausgabe 4/2008

Einloggen, um Zugang zu erhalten

Abstract

Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodegenerative disorders may prove to be useful as a therapeutic intervention. Creatine is a molecule that is produced both endogenously, and acquired exogenously through diet, and is an extremely important molecule that participates in buffering intracellular energy stores. Once creatine is transported into cells, creatine kinase catalyzes the reversible transphosphorylation of creatine via ATP to enhance the phosphocreatine energy pool. Creatine kinase enzymes are located at strategic intracellular sites to couple areas of high energy expenditure to the efficient regeneration of ATP. Thus, the creatinekinase/phosphocreatine system plays an integral role in energy buffering and overall cellular bioenergetics. Originally, exogenous creatine supplementation was widely used only as an ergogenic aid to increase the phosphocreatine pool within muscle to bolster athletic performance. However, the potential therapeutic value of creatine supplementation has recently been investigated with respect to various neurodegenerative disorders that have been associated with bioenergetic deficits as playing a role in disease etiology and/or progression which include; Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS), and Huntington’s disease. This review discusses the contribution of mitochondria and bioenergetics to the progression of these neurodegenerative diseases and investigates the potential neuroprotective value of creatine supplementation in each of these neurological diseases. In summary, current literature suggests that exogenous creatine supplementation is most efficacious as a treatment paradigm in Huntington’s and Parkinson’s disease but appears to be less effective for ALS and Alzheimer’s disease.

Adams, J. M., & Cory, S. (1998). The Bcl-2 protein family: Arbiters of cell survival. Science, 281, 1322–1326. doi:10.1126/science.281.5381.1322.PubMed

Adhihetty, P. J., & Hood, D. A. (2003). Mechanisms of apoptosis in skeletal muscle. Basic and applied myology, 13, 171–179.

Adhihetty, P. J., Irrcher, I., Joseph, A. M., Ljubicic, V., & Hood, D. A. (2003). Plasticity of skeletal muscle mitochondria in response to contractile activity. Experimental Physiology, 88, 99–107. doi:10.1113/eph8802505.PubMed

Aksenov, M., Aksenova, M., Butterfield, D. A., & Markesbery, W. R. (2000). Oxidative modification of creatine kinase BB in Alzheimer’s disease brain. Journal of Neurochemistry, 74, 2520–2527. doi:10.1046/j.1471-4159.2000.0742520.x.PubMed

Alston, T. A., Mela, L., & Bright, H. J. (1977). 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase. Proceedings of the National Academy of Sciences of the United States of America, 74, 3767–3771. doi:10.1073/pnas.74.9.3767.PubMed

Andreassen, O. A., Dedeoglu, A., Ferrante, R. J., Jenkins, B. G., Ferrante, K. L., Thomas, M., et al. (2001). Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington’s disease. Neurobiology of Disease, 8, 479–491. doi:10.1006/nbdi.2001.0406.PubMed

Andres, R. H., Ducray, A. D., Schlattner, U., Wallimann, T., & Widmer, H. R. (2008). Functions and effects of creatine in the central nervous system. Brain Research Bulletin, 76, 329–343. doi:10.1016/j.brainresbull.2008.02.035.PubMed

Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., et al. (2005). Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature, 434, 658–662. doi:10.1038/nature03434.PubMed

Baker, S. K., & Tarnopolsky, M. A. (2003). Targeting cellular energy production in neurological disorders. Expert Opinion on Investigational Drugs, 12, 1655–1679. doi:10.1517/13543784.12.10.1655.PubMed

Beal, M. F., Brouillet, E., Jenkins, B. G., Ferrante, R. J., Kowall, N. W., Miller, J. M., et al. (1993). Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. Journal of Neuroscience, 13, 4181–4192.PubMed

Beal, M. F. (1995). Aging, energy, and oxidative stress in neurodegenerative diseases. Annals of Neurology, 38, 357–366. doi:10.1002/ana.410380304.PubMed

Beal, M. F. (1996). Mitochondria, free radicals, and neurodegeneration. Current Opinion in Neurobiology, 6, 661–666. doi:10.1016/S0959-4388(96)80100-0.PubMed

Beal, M. F. (2000a). Mitochondria and the pathogenesis of ALS. Brain, 123(Pt 7), 1291–1292. doi:10.1093/brain/123.7.1291.PubMed

Beal, M. F. (2000b). Energetics in the pathogenesis of neurodegenerative diseases. Trends in Neurosciences, 23, 298–304. doi:10.1016/S0166-2236(00)01584-8.PubMed

Beal, M. F. (2000c). Limited-time exposure to mitochondrial toxins may lead to chronic progressive neurodegenerative diseases. Movement Disorders, 15, 434–435. doi:10.1002/1531-8257(200005)15:3<434::AID-MDS1002>3.0.CO;2-Q.PubMed

Beal, M. F. (2003). Bioenergetic approaches for neuroprotection in Parkinson’s disease. Annals of Neurology, 53(Suppl 3), S39–S47. doi:10.1002/ana.10479.PubMed

Beal, M. F., & Ferrante, R. J. (2004). Experimental therapeutics in transgenic mouse models of Huntington’s disease. Nature Reviews. Neuroscience, 5, 373–384. doi:10.1038/nrn1386.PubMed

Benzi, G., & Ceci, A. (2001). Creatine as nutritional supplementation and medicinal product. Journal of Sports Medicine and Physical Fitness, 41, 1–10.PubMed

Bessman, S. P., & Geiger, P. J. (1981). Transport of energy in muscle: The phosphorylcreatine shuttle. Science, 211, 448–452. doi:10.1126/science.6450446.PubMed

Bindoff, L. A., Birch-Machin, M., Cartlidge, N. E., Parker, W. D., Jr., & Turnbull, D. M. (1989). Mitochondrial function in Parkinson’s disease. Lancet, 2, 49. doi:10.1016/S0140-6736(89)90291-2.PubMed

Boero, J., Qin, W., Cheng, J., Woolsey, T. A., Strauss, A. W., & Khuchua, Z. (2003). Restricted neuronal expression of ubiquitous mitochondrial creatine kinase: Changing patterns in development and with increased activity. Molecular and Cellular Biochemistry, 244, 69–76. doi:10.1023/A:1022409101641.PubMed

Bogdanov, M. B., Ferrante, R. J., Kuemmerle, S., Klivenyi, P., & Beal, M. F. (1998a). Increased vulnerability to 3-nitropropionic acid in an animal model of Huntington’s disease. Journal of Neurochemistry, 71, 2642–2644.PubMed

Bogdanov, M. B., Ramos, L. E., Xu, Z., & Beal, M. F. (1998b). Elevated “hydroxyl radical” generation in vivo in an animal model of amyotrophic lateral sclerosis. Journal of Neurochemistry, 71, 1321–1324.PubMed

Brewer, G. J., & Wallimann, T. W. (2000). Protective effect of the energy precursor creatine against toxicity of glutamate and beta-amyloid in rat hippocampal neurons. Journal of Neurochemistry, 74, 1968–1978. doi:10.1046/j.1471-4159.2000.0741968.x.PubMed

Brouillet, E., Jenkins, B. G., Hyman, B. T., Ferrante, R. J., Kowall, N. W., Srivastava, R., et al. (1993). Age-dependent vulnerability of the striatum to the mitochondrial toxin 3-nitropropionic acid. Journal of Neurochemistry, 60, 356–359. doi:10.1111/j.1471-4159.1993.tb05859.x.PubMed

Brouillet, E., Hantraye, P., Ferrante, R. J., Dolan, R., Leroy-Willig, A., Kowall, N. W., et al. (1995). Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. Proceedings of the National Academy of Sciences of the United States of America, 92, 7105–7109. doi:10.1073/pnas.92.15.7105.PubMed

Browne, S. E., Bowling, A. C., MacGarvey, U., Baik, M. J., Berger, S. C., Muqit, M. M., et al. (1997). Oxidative damage and metabolic dysfunction in Huntington’s disease: Selective vulnerability of the basal ganglia. Annals of Neurology, 41, 646–653. doi:10.1002/ana.410410514.PubMed

Browne, S. E., Ferrante, R. J., & Beal, M. F. (1999). Oxidative stress in Huntington’s disease. Brain Pathology, 9, 147–163.PubMed

Burklen, T. S., Schlattner, U., Homayouni, R., Gough, K., Rak, M., Szeghalmi, A., et al. (2006). The Creatine Kinase/Creatine Connection to Alzheimer’s Disease: CK-Inactivation, APP-CK Complexes and Focal Creatine Deposits. Journal of Biomedicine and Biotechnology, 2006, 35936. doi:10.1155/JBB/2006/35936.PubMed

Butterfield, D. A., & Lauderback, C. M. (2002). Lipid peroxidation and protein oxidation in Alzheimer’s disease brain: Potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radical Biology and Medicine, 32, 1050–1060. doi:10.1016/S0891-5849(02)00794-3.PubMed

Candlish, E., La, C. J., & Unrau, A. M. (1969). The biosynthesis of 3-nitropropionic acid in creeping indigo (Indigofera spicata). Biochemistry, 8, 182–186. doi:10.1021/bi00829a026.PubMed

Carri, M. T., Ferri, A., Battistoni, A., Famhy, L., Gabbianelli, R., Poccia, F., et al. (1997). Expression of a Cu, Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2⁺ concentration in transfected neuroblastoma SH-SY5Y cells. FEBS Letters, 414, 365–368. doi:10.1016/S0014-5793(97)01051-X.PubMed

Castegna, A., Aksenov, M., Thongboonkerd, V., Klein, J. B., Pierce, W. M., Booze, R., et al. (2002a). Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part II: Dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. Journal of Neurochemistry, 82, 1524–1532. doi:10.1046/j.1471-4159.2002.01103.x.PubMed

Castegna, A., Aksenov, M., Aksenova, M., Thongboonkerd, V., Klein, J. B., Pierce, W. M., et al. (2002b). Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part I: Creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radical Biology and Medicine, 33, 562–571. doi:10.1016/S0891-5849(02)00914-0.PubMed

Ceddia, R. B., & Sweeney, G. (2004). Creatine supplementation increases glucose oxidation and AMPK phosphorylation and reduces lactate production in L6 rat skeletal muscle cells. Journal of Physiology, 555, 409–421.PubMed

Csukly, K., Ascah, A., Matas, J., Gardiner, P. F., Fontaine, E., & Burelle, Y. (2006). Muscle denervation promotes opening of the permeability transition pore and increases the expression of cyclophilin D. Journal of Physiology, 574, 319–327. doi:10.1113/jphysiol.2006.109702.PubMed

Cui, L., Jeong, H., Borovecki, F., Parkhurst, C. N., Tanese, N., & Krainc, D. (2006). Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell, 127, 59–69. doi:10.1016/j.cell.2006.09.015.PubMed

David, S., Shoemaker, M., & Haley, B. E. (1998). Abnormal properties of creatine kinase in Alzheimer’s disease brain: Correlation of reduced enzyme activity and active site photolabeling with aberrant cytosol-membrane partitioning. Brain Research. Molecular Brain Research, 54, 276–287. doi:10.1016/S0169-328X(97)00343-4.PubMed

de la Monte, S. M., Luong, T., Neely, T. R., Robinson, D., & Wands, J. R. (2000). Mitochondrial DNA damage as a mechanism of cell loss in Alzheimer’s disease. Laboratory Investigation, 80, 1323–1335. doi:10.1038/labinvest.3780140.PubMed

Dedeoglu, A., Kubilus, J. K., Yang, L., Ferrante, K. L., Hersch, S. M., Beal, M. F., et al. (2003). Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington’s disease transgenic mice. Journal of Neurochemistry, 85, 1359–1367. doi:10.1046/j.1471-4159.2003.01706.x.PubMed

Di Lisa, F., & Bernardi, P. (2006). Mitochondria and ischemia-reperfusion injury of the heart: Fixing a hole. Cardiovascular Research, 70, 191–199. doi:10.1016/j.cardiores.2006.01.016.PubMed

Dolder, M., Walzel, O., Speer, U., Schlattner, T., & Wallimann, T. (2003). Inhibition of the mitochondrial transition by creatine kinase substrates. Requirement for microcompartmentation. Journal of Biological Chemistry, 278, 17760–17766. doi:10.1074/jbc.M208705200.PubMed

Eppenberger, H. M., Dawson, D. M., & Kaplan, N. O. (1967). The comparative enzymology of creatine kinases. I. Isolation and characterization from chicken and rabbit tissues. Journal of Biological Chemistry, 242, 204–209.PubMed

Ferrante, R. J., Andreassen, O. A., Jenkins, B. G., Dedeoglu, A., Kuemmerle, S., Kubilus, J. K., et al. (2000). Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. Journal of Neuroscience, 20, 4389–4397.PubMed

Gallant, M., Rak, M., Szeghalmi, A., Del Bigio, M. R., Westaway, D., Yang, J., et al. (2006). Focally elevated creatine detected in amyloid precursor protein (APP) transgenic mice and Alzheimer disease brain tissue. Journal of Biological Chemistry, 281, 5–8. doi:10.1074/jbc.C500244200.PubMed

Green, D. R., & Reed, J. C. (1998). Mitochondria and apoptosis. Science, 281, 1309–1312. doi:10.1126/science.281.5381.1309.PubMed

Groeneveld, G. J., Van Kan, H. J., Kalmijn, S., Veldink, J. H., Guchelaar, H. J., Wokke, J. H., et al. (2003). Riluzole serum concentrations in patients with ALS: Associations with side effects and symptoms. Neurology, 61, 1141–1143.PubMed

Grunewald, T., & Beal, M. F. (1999). Bioenergetics in Huntington’s disease. Annals of the New York Academy of Sciences, 893, 203–213. doi:10.1111/j.1749-6632.1999.tb07827.x.PubMed

Gu, M., Gash, M. T., Mann, V. M., Javoy-Agid, F., Cooper, J. M., & Schapira, A. H. (1996). Mitochondrial defect in Huntington’s disease caudate nucleus. Annals of Neurology, 39, 385–389. doi:10.1002/ana.410390317.PubMed

Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., et al. (1994). Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science, 264, 1772–1775. doi:10.1126/science.8209258.PubMed

Henshaw, R., Jenkins, B. G., Schulz, J. B., Ferrante, R. J., Kowall, N. W., Rosen, B. R., et al. (1994). Malonate produces striatal lesions by indirect NMDA receptor activation. Brain Research, 647, 161–166. doi:10.1016/0006-8993(94)91412-5.PubMed

Hensley, K., Butterfield, D. A., Mattson, M., Aksenova, M., Harris, M., Wu, J. F., et al. (1995). A model for beta-amyloid aggregation and neurotoxicity based on the free radical generating capacity of the peptide: Implications of “molecular shrapnel” for Alzheimer’s disease. Proceedings of the Western Pharmacology Society, 38, 113–120.PubMed

Hersch, S. M., Gevorkian, S., Marder, K., Moskowitz, C., Feigin, A., Cox, M., et al. (2006). Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2’dG. Neurology, 66, 250–252. doi:10.1212/01.wnl.0000194318.74946.b6.PubMed

Hervias, I., Beal, M. F., & Manfredi, G. (2006). Mitochondrial dysfunction and amyotrophic lateral sclerosis. Muscle and Nerve, 33, 598–608. doi:10.1002/mus.20489.PubMed

Hoyer, S. (2004). Causes and consequences of disturbances of cerebral glucose metabolism in sporadic Alzheimer disease: Therapeutic implications. Advances in Experimental Medicine and Biology, 541, 135–152.PubMed

Jacobus, W. E., & Lehninger, A. L. (1973). Creatine kinase of rat heart mitochondria. Coupling of creatine phosphorylation to electron transport. Journal of Biological Chemistry, 248, 4803–4810.PubMed

Jenkins, B. G., Koroshetz, W. J., Beal, M. F., & Rosen, B. R. (1993). Evidence for impairment of energy metabolism in vivo in Huntington’s disease using localized 1H NMR spectroscopy. Neurology, 43, 2689–2695.PubMed

Jost, C. R., Van Der Zee, C. E., In ‘t Zandt, H. J., Oerlemans, F., Verheij, M., Streijger, F., et al. (2002). Creatine kinase B-driven energy transfer in the brain is important for habituation and spatial learning behaviour, mossy fibre field size and determination of seizure susceptibility. European Journal of Neuroscience, 15, 1692–1706.PubMed

Juhn, M. S., & Tarnopolsky, M. (1998a). Oral creatine supplementation and athletic performance: A critical review. Clinical Journal of Sport Medicine, 8, 286–297.PubMed

Juhn, M. S., & Tarnopolsky, M. (1998b). Potential side effects of oral creatine supplementation: A critical review. Clinical Journal of Sport Medicine, 8, 298–304.PubMedCrossRef

Klivenyi, P., Ferrante, R. J., Matthews, R. T., Bogdanov, M. B., Klein, A. M., Andreassen, O. A., et al. (1999). Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis. Nature Medicine, 5, 347–350. doi:10.1038/6568.PubMed

Kokoszka, J. E., Waymire, K. G., Levy, S. E., Sligh, J. E., Cai, J., Jones, D. P., et al. (2004). The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature, 427, 461–465. doi:10.1038/nature02229.PubMed

Koroshetz, W. J., Jenkins, B. G., Rosen, B. R., & Beal, M. F. (1997). Energy metabolism defects in Huntington’s disease and effects of coenzyme Q10. Annals of Neurology, 41, 160–165. doi:10.1002/ana.410410206.PubMed

Krige, D., Carroll, M. T., Cooper, J. M., Marsden, C. D., & Schapira, A. H. (1992). Platelet mitochondrial function in Parkinson’s disease. The Royal Kings and Queens Parkinson Disease Research Group. Annals of Neurology, 32, 782–788. doi:10.1002/ana.410320612.PubMed

Li, X., Burklen, T., Yuan, X., Schlattner, U., Desiderio, D. M., Wallimann, T., et al. (2006). Stabilization of ubiquitous mitochondrial creatine kinase preprotein by APP family proteins. Molecular and Cellular Neurosciences, 31, 263–272. doi:10.1016/j.mcn.2005.09.015.PubMed

Ludolph, A. C., He, F., Spencer, P. S., Hammerstad, J., & Sabri, M. (1991). 3-Nitropropionic acid-exogenous animal neurotoxin and possible human striatal toxin. Canadian Journal of Neurological Sciences, 18, 492–498.PubMed

Ludolph, A. C., Seelig, M., Ludolph, A. G., Sabri, M. I., & Spencer, P. S. (1992). ATP deficits and neuronal degeneration induced by 3-nitropropionic acid. Annals of the New York Academy of Sciences, 648, 300–302. doi:10.1111/j.1749-6632.1992.tb24562.x.PubMed

Mahoney, D. J., Parise, G., & Tarnopolsky, M. A. (2002). Nutritional and exercise-based therapies in the treatment of mitochondrial disease. Current Opinion in Clinical Nutrition and Metabolic Care, 5, 619–629. doi:10.1097/00075197-200211000-00004.PubMed

Markesbery, W. R. (1997). Oxidative stress hypothesis in Alzheimer’s disease. Free Radical Biology and Medicine, 23, 134–147. doi:10.1016/S0891-5849(96)00629-6.PubMed

Matthews, R. T., Yang, L., Jenkins, B. G., Ferrante, R. J., Rosen, B. R., Kaddurah-Daouk, R., et al. (1998). Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington’s disease. Journal of Neuroscience, 18, 156–163.PubMed

Matthews, R. T., Ferrante, R. J., Klivenyi, P., Yang, L., Klein, A. M., Mueller, G., et al. (1999). Creatine and cyclocreatine attenuate MPTP neurotoxicity. Experimental Neurology, 157, 142–149. doi:10.1006/exnr.1999.7049.PubMed

Maurer, I., Zierz, S., & Moller, H. J. (2000). A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiology of Aging, 21, 455–462. doi:10.1016/S0197-4580(00)00112-3.PubMed

Mihic, S., MacDonald, J. R., McKenzie, S., & Tarnopolsky, M. A. (2000). Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Medicine and Science in Sports and Exercise, 32, 291–296. doi:10.1097/00005768-200002000-00007.PubMed

NINDS NET-PD Investigators. (2006). A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology, 66, 664–671. doi:10.1212/01.wnl.0000201252.57661.e1.

O’Gorman, E., Piendl, T., Muller, M., Brdiczka, D., & Wallimann, T. (1997a). Mitochondrial intermembrane inclusion bodies: The common denominator between human mitochondrial myopathies and creatine depletion, due to impairment of cellular energetics. Molecular and Cellular Biochemistry, 174, 283–289. doi:10.1023/A:1006881113149.PubMed

O’Gorman, E., Beutner, G., Dolder, M., Koretsky, A. P., Brdiczka, D., & Wallimann, T. (1997b). The role of creatine kinase in inhibition of mitochondrial permeability transition. FEBS Letters, 414, 253–257. doi:10.1016/S0014-5793(97)01045-4.PubMed

Onyango, I. G., & Khan, S. M. (2006). Oxidative stress, mitochondrial dysfunction, and stress signaling in Alzheimer’s disease. Current Alzheimer Research, 3, 339–349. doi:10.2174/156720506778249489.PubMed

Palfi, S., Ferrante, R. J., Brouillet, E., Beal, M. F., Dolan, R., Guyot, M. C., et al. (1996). Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington’s disease. Journal of Neuroscience, 16, 3019–3025.PubMed

Parker, W. D., Jr, Boyson, S. J., & Parks, J. K. (1989). Abnormalities of the electron transport chain in idiopathic Parkinson’s disease. Annals of Neurology, 26, 719–723. doi:10.1002/ana.410260606.PubMed

Parker, W. D., Jr. (1991). Cytochrome oxidase deficiency in Alzheimer’s disease. Annals of the New York Academy of Sciences, 640, 59–64.PubMed

Peng, T. I., & Greenamyre, J. T. (1998). Privileged access to mitochondria of calcium influx through N-methyl-d-aspartate receptors. Molecular Pharmacology, 53, 974–980.PubMed

Persky, A. M., & Brazeau, G. A. (2001). Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacological Reviews, 53, 161–176.PubMed

Pettegrew, J. W., Panchalingam, K., Klunk, W. E., McClure, R. J., & Muenz, L. R. (1994). Alterations of cerebral metabolism in probable Alzheimer’s disease: A preliminary study. Neurobiology of Aging, 15, 117–132. doi:10.1016/0197-4580(94)90152-X.PubMed

Phukan, J., Pender, N. P., & Hardiman, O. (2007). Cognitive impairment in amyotrophic lateral sclerosis. Lancet Neurology, 6, 994–1003. doi:10.1016/S1474-4422(07)70265-X.PubMed

Poortmans, J. R., Auquier, H., Renaut, V., Durussel, A., Saugy, M., & Brisson, G. R. (1997). Effect of short-term creatine supplementation on renal responses in men. European Journal of Applied Physiology and Occupational Physiology, 76, 566–567. doi:10.1007/s004210050291.PubMed

Poortmans, J. R., & Francaux, M. (2000). Adverse effects of creatine supplementation: Fact or fiction? Sports Medicine, 30, 155–170. doi:10.2165/00007256-200030030-00002.PubMed

Primeau, A. J., Adhihetty, P. J., & Hood, D. A. (2002). Apoptosis in heart and skeletal muscle. Canadian Journal of Applied Physiology, 27, 349–395.PubMed

Rae, C., Digney, A. L., McEwan, S. R., & Bates, T. C. (2003). Oral creatine monohydrate supplementation improves brain performance: A double-blind, placebo-controlled, cross-over trial. Proceedings. Biological Sciences, 270, 2147–2150. doi:10.1098/rspb.2003.2492.

Robinson, T. M., Sewell, D. A., Casey, A., Steenge, G., & Greenhaff, P. L. (2000). Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. British Journal of Sports Medicine, 34, 284–288. doi:10.1136/bjsm.34.4.284.PubMed

Ryu, H., & Ferrante, R. J. (2005). Emerging chemotherapeutic strategies for Huntington’s disease. Expert Opinion on Emerging Drugs, 10, 345–363. doi:10.1517/14728214.10.2.345.PubMed

Saks, V. A., Rosenshtraukh, L. V., Smirnov, V. N., & Chazov, E. I. (1978). Role of creatine phosphokinase in cellular function and metabolism. Canadian Journal of Physiology and Pharmacology, 56, 691–706.PubMed

Schapira, A. H., Cooper, J. M., Dexter, D., Clark, J. B., Jenner, P., & Marsden, C. D. (1990). Mitochondrial complex I deficiency in Parkinson’s disease. Journal of Neurochemistry, 54, 823–827. doi:10.1111/j.1471-4159.1990.tb02325.x.PubMed

Schlattner, U., Tokarska-Schlattner, M., & Wallimann, T. (2006). Mitochondrial creatine kinase in human health and disease. Biochimica et Biophysica Acta, 1762, 164–180.PubMed

Schulz, J. B., & Beal, M. F. (1995). Neuroprotective effects of free radical scavengers and energy repletion in animal models of neurodegenerative disease. Annals of the New York Academy of Sciences, 765, 100–110. doi:10.1111/j.1749-6632.1995.tb16565.x.PubMed

Selkoe, D. J. (1999). Translating cell biology into therapeutic advances in Alzheimer’s disease. Nature, 399, A23–A31. doi:10.1038/19866.PubMed

Shefner, J. M., Cudkowicz, M. E., Schoenfeld, D., Conrad, T., Taft, J., Chilton, M., et al. (2004). A clinical trial of creatine in ALS. Neurology, 63, 1656–1661.PubMed

Simon, D. K., & Johns, D. R. (1999). Mitochondrial disorders: Clinical and genetic features. Annual Review of Medicine, 50, 111–127. doi:10.1146/annurev.med.50.1.111.PubMed

Small, D. H., & McLean, C. A. (1999). Alzheimer’s disease and the amyloid beta protein: What is the role of amyloid? Journal of Neurochemistry, 73, 443–449. doi:10.1046/j.1471-4159.1999.0730443.x.PubMed

Smith, C. D., Carney, J. M., Starke-Reed, P. E., Oliver, C. N., Stadtman, E. R., Floyd, R. A., et al. (1991). Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 88, 10540–10543. doi:10.1073/pnas.88.23.10540.PubMed

Sora, I., Richman, J., Santoro, G., Wei, H., Wang, Y., Vanderah, T., et al. (1994). The cloning and expression of a human creatine transporter. Biochemical and Biophysical Research Communications, 204, 419–427. doi:10.1006/bbrc.1994.2475.PubMed

Steeghs, K., Benders, A., Oerlemans, F., de, H. A., Heerschap, A., Ruitenbeek, W., et al. (1997). Altered Ca2⁺ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. Cell, 89, 93–103. doi:10.1016/S0092-8674(00)80186-5.PubMed

Steenge, G. R., Lambourne, J., Casey, A., Macdonald, I. A., & Greenhaff, P. L. (1998). Stimulatory effect of insulin on creatine accumulation in human skeletal muscle. American Journal of Physiology, 275, E974–E979.PubMed

Stockler, S., Marescau, B., De Deyn, P. P., Trijbels, J. M., & Hanefeld, F. (1997). Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism, 46, 1189–1193. doi:10.1016/S0026-0495(97)90215-8.PubMed

Stockler, S., & Hanefeld, F. (1997). Guanidinoacetate methyltransferase deficiency: A newly recognized inborn error of creatine biosynthesis. Wiener Klinische Wochenschrift, 109, 86–88.PubMed

Streijger, F., Oerlemans, F., Ellenbroek, B. A., Jost, C. R., Wieringa, B., & Van Der Zee, C. E. (2005). Structural and behavioural consequences of double deficiency for creatine kinases BCK and UbCKmit. Behavioural Brain Research, 157, 219–234. doi:10.1016/j.bbr.2004.07.002.PubMed

Tarnopolsky, M. A., & Beal, M. F. (2001). Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Annals of Neurology, 49, 561–574. doi:10.1002/ana.1028.PubMed

Tarnopolsky, M. A., & Safdar, A. (2008). The potential benefits of creatine and conjugated linoleic acid as adjuncts to resistance training in older adults. Applied Physiology, Nutrition, and Metabolism, 33, 213–227. doi:10.1139/H07-142.PubMed

Thomas, B., & Beal, M. F. (2007). Parkinson’s disease. Human Molecular Genetics, 16(Spec no. 2), R183–R194.PubMed

Valla, J., Berndt, J. D., & Gonzalez-Lima, F. (2001). Energy hypometabolism in posterior cingulate cortex of Alzheimer’s patients: Superficial laminar cytochrome oxidase associated with disease duration. Journal of Neuroscience, 21, 4923–4930.PubMed

van der Knaap, M. S., Verhoeven, N. M., Maaswinkel-Mooij, P., Pouwels, P. J., Onkenhout, W., Peeters, E. A., et al. (2000). Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect. Annals of Neurology, 47, 540–543. doi:10.1002/1531-8249(200004)47:4<540::AID-ANA23>3.0.CO;2-K.PubMed

Wallimann, T., Wyss, M., Brdiczka, D., Nicolay, K., & Eppenberger, H. M. (1992). Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: The ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochemical Journal, 281(Pt 1), 21–40.PubMed

Wallimann, T., & Hemmer, W. (1994). Creatine kinase in non-muscle tissues and cells. Molecular and Cellular Biochemistry, 133–134, 193–220. doi:10.1007/BF01267955.PubMed

Watanabe, A., Kato, N., & Kato, T. (2002). Effects of creatine on mental fatigue and cerebral hemoglobin oxygenation. Neuroscience Research, 42, 279–285. doi:10.1016/S0168-0102(02)00007-X.PubMed

Weydt, P., Pineda, V. V., Torrence, A. E., Libby, R. T., Satterfield, T. F., Lazarowski, E. R., et al. (2006). Thermoregulatory and metabolic defects in Huntington’s disease transgenic mice implicate PGC-1alpha in Huntington’s disease neurodegeneration. Cell Metabolism, 4, 349–362. doi:10.1016/j.cmet.2006.10.004.PubMed

Wong, P. C., Pardo, C. A., Borchelt, D. R., Lee, M. K., Copeland, N. G., Jenkins, N. A., et al. (1995). An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron, 14, 1105–1116. doi:10.1016/0896-6273(95)90259-7.PubMed

Wyss, M., & Schulze, A. (2002). Health implications of creatine: Can oral creatine supplementation protect against neurological and atherosclerotic disease? Neuroscience, 112, 243–260. doi:10.1016/S0306-4522(02)00088-X.PubMed

Zong, H., Ren, J. M., Young, L. H., Pypaert, M., Mu, J., Birnbaum, M. J., et al. (2002). AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proceedings of the National Academy of Sciences of the United States of America, 99, 15983–15987. doi:10.1073/pnas.252625599.PubMed

Titel: Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases
verfasst von: Peter J. Adhihetty
M. Flint Beal
Publikationsdatum: 01.12.2008
Verlag: Humana Press Inc
Erschienen in: NeuroMolecular Medicine / Ausgabe 4/2008
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-008-8053-y

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

18.04.2024 | Arterielle Hypertonie | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases

Abstract

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Manche Gestagene können das Risiko für Meningeome erhöhen

Parkinson: Größere Studie bestätigt Genauigkeit von Hauttest

Update Neurologie

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2008

Hormetic Dietary Phytochemicals

BACE1 Polymorphisms Do Not Influence Platelet Membrane β-secretase Activity or Genetic Susceptibility for Alzheimer’s Disease in the Northern Irish Population

Integrin β4 in Neural Cells

Coupling Endoplasmic Reticulum Stress to the Cell Death Program in Dopaminergic Cells: Effect of Paraquat

Genetic Variation in the α7 Nicotinic Acetylcholine Receptor is Associated with Delusional Symptoms in Alzheimer’s Disease

Botanical Phenolics and Brain Health

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

Manche Gestagene können das Risiko für Meningeome erhöhen

Parkinson: Größere Studie bestätigt Genauigkeit von Hauttest

Update Neurologie