Monograph

New insights into creatine transporter deficiency

Identification of neuropathological and metabolic targets for treatment
  • Angelo Molinaro,

Creatine (Cr) transporter deficiency (CCDS1) is a very rare and severe condition due to impaired energetic metabolism. In this work we showed for the first time the following facts: this diseases is a progressive neurodegenerative disorder in which a set of maladaptive compensatory mechanisms leads to a progressive damage of brain functions; cell energy metabolism and mitochondria seem strongly involved in the pathogenesis and they could represent useful potential targets for therapeutic interventions; inflammation seems to play an important part in this progressive damage, and this observation can pave the way to treatment strategies; neural circuits disruption involving inhibitory systems could give a huge contribute to many of the clinical aspects observed in patients, as epilepsy and cognitive impairment, since the excitatory/inhibitory balance is fundamental for the normal function of neural circuits. Factors outside the CNS are important in the pathogenesis of at least some aspects of the disorder, since the conditional KO model show difference in the timing of onset of some cognitive defects and in the presence of stereotypies.

  • Keywords:
  • creatine,
  • transporter,
  • brain,
+ Show more
Purchase

Angelo Molinaro

Università di Firenze - ORCID: 0000-0003-1690-5448

Angelo Molinaro earned an MD at University of Pisa in 2009 (cum laude) and subsequently the title of Specialist in Endocrinology and Metabolic disorders (cum laude, at University of Pisa). He was Research Fellow at Harvard Medical School and Massachusetts General Hospital, with Prof. Jüppner studying the molecular genetics of rare endocrine diseases. He worked at the Free University of Bruxelles in the lab of the Prof. Sabine Costagliola studying the cellular and molecular embryology of early thyroid development. Subsequently, earned a PhD in Neuroscience (with distinction) at the University of Florence in the lab of Prof. Tommaso Pizzorusso (Institute of Neuroscience, CNR in Pisa) and in Paris at the Institute for Brain and Spinal Cord affiliated to Sorbonne Université with Prof. Alberto Bacci and Prof. Laurence Cathala.
  1. Ahmed, Z., Sheng, H., Xu, Y., Lin, W.-L., Innes, A. E., Gass, J., Yu, X., Hou, H., Chiba, S., Yamanouchi, K., Leissring, M., Petrucelli, L., Nishihara, M., Hutton, M. L., McGowan, E., Dickson, D. W., Lewis, J. and Lewis, J. (2010) ‘Accelerated Lipofuscinosis and Ubiquitination in Granulin Knockout Mice Suggest a Role for Progranulin in Successful Aging’, The American Journal of Pathology, 177(1), pp. 311–324. . DOI: 10.2353/ajpath.2010.090915
  2. Alcaide, P., Merinero, B., Ruiz-Sala, P., Richard, E., Navarrete, R., Arias, Á., Ribes, A., Artuch, R., Campistol, J., Ugarte, M. and Rodríguez-Pombo, P. (2011) ‘Defining the pathogenicity of creatine deficiency syndrome’, Human Mutation. Wiley-Blackwell, 32(3), pp. 282–291. DOI: 10.1002/humu.21421
  3. Alessandrì, M. G., Celati, L., Battini, R., Casarano, M. and Cioni, G. (2005) ‘Gas chromatography/mass spectrometry assay for arginine: Glycine-amidinotransferase deWciency’, ANALYTICAL BIOCHEMISTRY, 343, pp. 356–358. DOI: 10.1016/j.ab.2005.05.003
  4. Almeida, L. S., Salomons, G. S., Hogenboom, F., Jakobs, C. and Schoffelmeer, A. N. M. (2006) ‘Exocytotic release of creatine in rat brain.’, Synapse (New York, N.Y.), 60(2), pp. 118–23. DOI: 10.1002/syn.20280
  5. Andres, R. H., Ducray, A. D., Schlattner, U., Wallimann, T. and Widmer, H. R. (2008) ‘Functions and effects of creatine in the central nervous system.’, Brain research bulletin, 76(4), pp. 329–43. DOI: 10.1016/j.brainresbull.2008.02.035
  6. Anselm, I. M., Alkuraya, F. S., Salomons, G. S., Jakobs, C., Fulton, A. B., Mazumdar, M., Rivkin, M., Frye, R., Poussaint, T. Y., Marsden, D. and Marsden, D. (2006) ‘X-linked creatine transporter defect: A report on two unrelated boys with a severe clinical phenotype’, Journal of Inherited Metabolic Disease, 29(1), pp. 214–219. DOI: 10.1007/s10545-006-0123-4
  7. Assunção, M., Santos-Marques, M. J., Carvalho, F., Lukoyanov, N. V. and Andrade, J. P. (2011) ‘Chronic green tea consumption prevents age-related changes in rat hippocampal formation’, Neurobiology of Aging, 32(4), pp. 707–717. DOI: 10.1016/j.neurobiolaging.2009.03.016
  8. Balsom, P. D., Söderlund, K. and Ekblom, B. (1994) ‘Creatine in humans with special reference to creatine supplementation.’, Sports medicine (Auckland, N.Z.), 18(4), pp. 268–80. DOI: 10.2165/00007256-199418040-00005
  9. Bamburg, J. R. and Bernstein, B. W. (2016) ‘Actin dynamics and cofilin-actin rods in alzheimer disease’, Cytoskeleton, 73(9), pp. 477–497. DOI: 10.1002/cm.21282
  10. Bano, D., Agostini, M., Melino, G. and Nicotera, P. (2011) ‘Ageing, Neuronal Connectivity and Brain Disorders: An Unsolved Ripple Effect’, Molecular Neurobiology, 43(2), pp. 124–130. DOI: 10.1007/s12035-011-8164-6
  11. Baroncelli, L., Alessandrì, M. G., Tola, J., Putignano, E., Migliore, M., Amendola, E., Gross, C., Leuzzi, V., Cioni, G. and Pizzorusso, T. (2014) ‘A novel mouse model of creatine transporter deficiency.’, F1000Research, 3(0), p. 228. DOI: 10.12688/f1000research.5369.1
  12. Bartsch, T. and Wulff, P. (2015) ‘The hippocampus in aging and disease: From plasticity to vulnerability’, Neuroscience, 309, pp. 1–16. DOI: 10.1016/j.neuroscience.2015.07.084
  13. Beck, H., Flynn, K., Lindenberg, K. S., Schwarz, H., Bradke, F., Di Giovanni, S. and Knoll, B. (2012) ‘Serum Response Factor (SRF)-cofilin-actin signaling axis modulates mitochondrial dynamics’, Proceedings of the National Academy of Sciences, 109(38), pp. E2523–E2532. DOI: 10.1073/pnas.1208141109
  14. Bender, A., Beckers, J., Schneider, I., Hölter, S. M., Haack, T., Ruthsatz, T., Vogt-Weisenhorn, D. M., Becker, L., Genius, J., Rujescu, D., Irmler, M., Mijalski, T., Mader, M., Quintanilla-Martinez, L., Fuchs, H., Gailus-Durner, V., de Angelis, M. H., Wurst, W., Schmidt, J. and Klopstock, T. (2008) ‘Creatine improves health and survival of mice’, Neurobiology of Aging, 29(9), pp. 1404–1411. DOI: 10.1016/j.neurobiolaging.2007.03.001
  15. Betsalel, O. T., Pop, A., Rosenberg, E. H., Fernandez-Ojeda, M., Creatine Transporter Research, Group, C., Jakobs, C. and Salomons, G. S. (2012) ‘Detection of variants in SLC6A8 and functional analysis of unclassified missense variants.’, Molecular genetics and metabolism, 105(4), pp. 596–601. DOI: 10.1016/j.ymgme.2011.12.022
  16. Bizzi, A., Bugiani, M., Salomons, G. S., Hunneman, D. H., Moroni, I., Estienne, M., Danesi, U., Jakobs, C. and Uziel, G. (2002) ‘X-linked creatine deficiency syndrome: A novel mutation in creatine transporter geneSLC6A8’, Annals of Neurology, 52(2), pp. 227–231. DOI: 10.1002/ana.10246
  17. Bories, C., Husson, Z., Guitton, M. J. and De Koninck, Y. (2013) ‘Differential balance of prefrontal synaptic activity in successful versus unsuccessful cognitive aging.’, The Journal of neuroscience : the official journal of the Society for Neuroscience, 33(4), pp. 1344–56. DOI: 10.1523/JNEUROSCI.3258-12.2013
  18. Braissant, O., Cagnon, L., Monnet-Tschudi, F., Speer, O., Wallimann, T., Honegger, P. and Henry, H. (2008) ‘Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency’, European Journal of Neuroscience, 27(7), pp. 1673–1685. DOI: 10.1111/j.1460-9568.2008.06126.x
  19. Braissant, O., Henry, H., Loup, M., Eilers, B. and Bachmann, C. (2001) ‘Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study.’, Brain research. Molecular brain research, 86(1–2), pp. 193–201. DOI: 10.1016/s0169-328x(00)00269-2
  20. Braissant, O., Henry, H., Villard, A.-M., Speer, O., Wallimann, T. and Bachmann, C. (2005) ‘Creatine synthesis and transport during rat embryogenesis: spatiotemporal expression of AGAT, GAMT and CT1.’, BMC Developmental Biology, 5(1), p. 9. DOI: 10.1186/1471-213X-5-9
  21. Brandenstein, L., Schweizer, M., Sedlacik, J., Fiehler, J. and Storch, S. (2016) ‘Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7’, Human Molecular Genetics, 25(4), pp. 777–791. DOI: 10.1093/hmg/ddv615
  22. Brosnan, J. T. and Brosnan, M. E. (2007) ‘Creatine: Endogenous Metabolite, Dietary, and Therapeutic Supplement’, Annual Review of Nutrition, 27(1), pp. 241–261. DOI: 10.1146/annurev.nutr.27.061406.093621
  23. Brynczka, C. and Merrick, B. A. (2008) ‘The p53 transcriptional target gene wnt7b contributes to NGF-inducible neurite outgrowth in neuronal PC12 cells’, Differentiation, 76(7), pp. 795–808. DOI: 10.1111/j.1432-0436.2007.00261.x
  24. Carducci, C., Carducci, C., Santagata, S., Adriano, E., Artiola, C., Thellung, S., Gatta, E., Robello, M., Florio, T., Antonozzi, I., Leuzzi, V. and Balestrino, M. (2012) ‘In vitro study of uptake and synthesis of creatine and its precursors by cerebellar granule cells and astrocytes suggests some hypotheses on the physiopathology of the inherited disorders of creatine metabolism.’, BMC neuroscience. BioMed Central, 13, p. 41. DOI: 10.1186/1471-2202-13-41
  25. Chanutin, A. (1926) ‘Tha fate of creatine when administered to man’, The Journal of biological chemistry, (2).
  26. Chen, B. and Wang, Y. (2015) ‘Cofilin rod formation in neurons impairs neuronal structure and function.’, CNS & neurological disorders drug targets, 14(4), pp. 554–60. DOI: 10.2174/1871527314666150225144052
  27. Chilosi, A., Casarano, M., Comparini, A., Battaglia, F., Mancardi, M., Schiaffino, C., Tosetti, M., Leuzzi, V., Battini, R. and Cioni, G. (2012) ‘Neuropsychological profile and clinical effects of arginine treatment in children with creatine transport deficiency’, Orphanet Journal of Rare Diseases, 7(1), p. 43. DOI: 10.1186/1750-1172-7-43
  28. Chilosi, A., Leuzzi, V., Battini, R., Tosetti, M., Ferretti, G., Comparini, A., Casarano, M., Moretti, E., Alessandri, M. G., Bianchi, M. C. and Cioni, G. (2008) ‘Treatment with L-arginine improves neuropsychological disorders in a child with creatine transporter defect.’, Neurocase, 14(2), pp. 151–61. DOI: 10.1080/13554790802060821
  29. Choe, C., Nabuurs, C., Stockebrand, M. C., Neu, A., Nunes, P., Morellini, F., Sauter, K., Schillemeit, S., Hermans-Borgmeyer, I., Marescau, B., Heerschap, A. and Isbrandt, D. (2013) ‘l-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome’, Human Molecular Genetics. Oxford University Press, 22(1), pp. 110–123. DOI: 10.1093/hmg/dds407
  30. Christian, K. M., Song, H. and Ming, G. (2014) ‘Functions and Dysfunctions of Adult Hippocampal Neurogenesis’, Annual Review of Neuroscience, 37(1), pp. 243–262. DOI: 10.1146/annurev-neuro-071013-014134
  31. Ciregia, F., Bugliani, M., Ronci, M., Giusti, L., Boldrini, C., Mazzoni, M. R., Mossuto, S., Grano, F., Cnop, M., Marselli, L., Giannaccini, G., Urbani, A., Lucacchini, A. and Marchetti, P. (2017) ‘Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets.’, Scientific reports, 7(1), p. 13445. DOI: 10.1038/s41598-017-13908-w
  32. Ciregia, F., Giusti, L., Da Valle, Y., Donadio, E., Consensi, A., Giacomelli, C., Sernissi, F., Scarpellini, P., Maggi, F., Lucacchini, A. and Bazzichi, L. (2013) ‘A multidisciplinary approach to study a couple of monozygotic twins discordant for the chronic fatigue syndrome: a focus on potential salivary biomarkers’, Journal of Translational Medicine, 11(1), p. 243. DOI: 10.1186/1479-5876-11-243
  33. deGrauw, T. J., Cecil, K. M., Byars, A. W., Salomons, G. S., Ball, W. S. and Jakobs, C. (2003) ‘The clinical syndrome of creatine transporter deficiency.’, Molecular and cellular biochemistry, 244(1–2), pp. 45–8.
  34. Depino, A. M. (2013) ‘Peripheral and central inflammation in autism spectrum disorders’, Molecular and Cellular Neuroscience, 53, pp. 69–76 DOI: 10.1016/j.mcn.2012.10.003
  35. Di Giovanni, S. and Rathore, K. (2012) ‘p53-dependent pathways in neurite outgrowth and axonal regeneration’, Cell and Tissue Research, 349(1), pp. 87–95. DOI: 10.1007/s00441-011-1292-5
  36. di Salvo, M. L., Mastrangelo, M., Nogués, I., Tolve, M., Paiardini, A., Carducci, C., Mei, D., Montomoli, M., Tramonti, A., Guerrini, R., Contestabile, R. and Leuzzi, V. (2017) ‘Pyridoxine-5’-phosphate oxidase (Pnpo) deficiency: Clinical and biochemical alterations associated with the C.347g>A (P.·Arg116gln) mutation.’, Molecular genetics and metabolism. Elsevier, 122(1–2), pp. 135–142. DOI: 10.1016/j.ymgme.2017.08.003
  37. Diaz-Beltran, L., Esteban, F. J. and Wall, D. P. (2016) ‘A common molecular signature in ASD gene expression: following Root 66 to autism’, Translational Psychiatry. Nature Publishing Group, 6(1), pp. e705–e705 DOI: 10.1038/tp.2015.112
  38. Dodd, J. R., Birch, N. P., Waldvogel, H. J. and Christie, D. L. (2010) ‘Functional and immunocytochemical characterization of the creatine transporter in rat hippocampal neurons.’, Journal of neurochemistry, 115(3), pp. 684–93. DOI: 10.1111/j.1471-4159.2010.06957.x
  39. Dunlop, R. A., Brunk, U. T. and Rodgers, K. J. (2009) ‘Oxidized proteins: Mechanisms of removal and consequences of accumulation’, IUBMB Life, pp. 522–527. DOI: 10.1002/iub.189
  40. Ebadi, M. and Klangkalya, B. (1979) ‘On the mechanism of pyridoxal phosphate-related convulsions as implicated in enhanced transport of GABA.’, Neuropharmacology, 18(3), pp. 301–7. DOI: 10.1016/0028-3908(79)90130-8
  41. Edvardson, S., Korman, S. H., Livne, A., Shaag, A., Saada, A., Nalbandian, R., Allouche-Arnon, H., Gomori, J. M. and Katz-Brull, R. (2010) ‘l-arginine:glycine amidinotransferase (AGAT) deficiency: Clinical presentation and response to treatment in two patients with a novel mutation’, Molecular Genetics and Metabolism, 101(2–3), pp. 228–232. DOI: 10.1016/j.ymgme.2010.06.021
  42. Enrico, A., Patrizia, G., Luisa, P., Alessandro, P., Gianluigi, L., Carlo, G. and Maurizio, B. (2013) ‘Electrophysiology and biochemical analysis of cyclocreatine uptake and effect in hippocampal slices’, Journal of Integrative Neuroscience, 12(02), pp. 285–297. DOI: 10.1142/S0219635213500155
  43. Etherton, M. R., Blaiss, C. A., Powell, C. M. and Sudhof, T. C. (2009) ‘Mouse neurexin-1 deletion causes correlated electrophysiological and behavioral changes consistent with cognitive impairments’, Proceedings of the National Academy of Sciences, 106(42), pp. 17998–18003. DOI: 10.1073/pnas.0910297106
  44. Evangeliou, A., Vasilaki, K., Karagianni, P. and Nikolaidis, N. (2009) ‘Clinical applications of creatine supplementation on paediatrics.’, Current pharmaceutical biotechnology, 10(7), pp. 683–90. DOI: 10.2174/138920109789542075
  45. Fons, C., Arias, A., Sempere, A., Póo, P., Pineda, M., Mas, A., López-Sala, A., Garcia-Villoria, J., Vilaseca, M. A., Ozaez, L., Lluch, M., Artuch, R., Campistol, J. and Ribes, A. (2010) ‘Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency’, Molecular Genetics and Metabolism, 99(3), pp. 296–299. DOI: 10.1016/j.ymgme.2009.10.186
  46. Franceschi, C., Bonafè, M., Valensin, S., Olivieri, F., De Luca, M., Ottaviani, E. and De Benedictis, G. (2006) ‘Inflamm-aging: An Evolutionary Perspective on Immunosenescence’, Annals of the New York Academy of Sciences. Wiley/Blackwell (10.1111), 908(1), pp. 244–254. DOI: 10.1111/j.1749-6632.2000.tb06651.x
  47. Fuccillo, M. V. (2016) ‘Striatal Circuits as a Common Node for Autism Pathophysiology’, Frontiers in Neuroscience, 10, p. 27 DOI: 10.3389/fnins.2016.00027
  48. García-Delgado, M., Peral, M. J., Cano, M., Calonge, M. L. and Ilundáin, A. A. (2001) ‘Creatine transport in brush-border membrane vesicles isolated from rat kidney cortex.’, Journal of the American Society of Nephrology : JASN, 12(9), pp. 1819–25.
  49. Giusti, S. A., Vercelli, C. A., Vogl, A. M., Kolarz, A. W., Pino, N. S., Deussing, J. M. and Refojo, D. (2014) ‘Behavioral phenotyping of Nestin-Cre mice: Implications for genetic mouse models of psychiatric disorders’, Journal of Psychiatric Research, 55, pp. 87–95. DOI: 10.1016/j.jpsychires.2014.04.002
  50. Gori, Z., De Tata, V., Pollera, M. and Bergamini, E. (1988) ‘Mitochondrial myopathy in rats fed with a diet containing beta-guanidine propionic acid, an inhibitor of creatine entry in muscle cells.’, British journal of experimental pathology. Wiley-Blackwell, 69(5), pp. 639–50.
  51. Gospe, S. M., Olin, K. L. and Keen, C. L. (1994) ‘Reduced GABA synthesis in pyridoxine-dependent seizures.’, Lancet (London, England), 343(8906), pp. 1133–4. DOI: 10.1016/s0140-6736(94)90236-4
  52. Grissom, N. M., McKee, S. E., Schoch, H., Bowman, N., Havekes, R., O’Brien, W. T., Mahrt, E., Siegel, S., Commons, K., Portfors, C., Nickl-Jockschat, T., Reyes, T. M. and Abel, T. (2018) ‘Male-specific deficits in natural reward learning in a mouse model of neurodevelopmental disorders’, Molecular Psychiatry, 23(3), pp. 544–555. DOI: 10.1038/mp.2017.184
  53. Guimbal, C. and Kilimann, M. W. (1993) ‘A Na(+)-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression.’, The Journal of biological chemistry, 268(12), pp. 8418–21.
  54. Haffernan, C. (2015) Creatine: a short history
  55. Hathaway, S. C., Friez, M., Limbo, K., Parker, C., Salomons, G. S., Vockley, J., Wood, T. and Abdul-Rahman, O. A. (2010) ‘X-Linked Creatine Transporter Deficiency Presenting as a Mitochondrial Disorder’, Journal of Child Neurology, 25(8), pp. 1009–1012. DOI: 10.1177/0883073809352109
  56. Head, E., Lott, I. T., Wilcock, D. M. and Lemere, C. A. (2016) ‘Aging in Down Syndrome and the Development of Alzheimer’s Disease Neuropathology.’, Current Alzheimer research, 13(1), pp. 18–29. DOI: 10.2174/1567205012666151020114607
  57. Hefendehl, J. K., Neher, J. J., Sühs, R. B., Kohsaka, S., Skodras, A. and Jucker, M. (2014) ‘Homeostatic and injury-induced microglia behavior in the aging brain’, Aging Cell. Wiley/Blackwell (10.1111), 13(1), pp. 60–69. DOI: 10.1111/acel.12149
  58. Hoffmann, H. and Schiene-Fischer, C. (2014) ‘Functional aspects of extracellular cyclophilins’, Biological Chemistry, 395(7–8), pp. 721–35. DOI: 10.1515/hsz-2014-0125
  59. Höhn, A. and Grune, T. (2013) ‘Lipofuscin: formation, effects and role of macroautophagy.’, Redox biology. Elsevier, 1(1), pp. 140–4. DOI: 10.1016/j.redox.2013.01.006
  60. Ippolito, D. M. and Eroglu, C. (2010) ‘Quantifying Synapses: an Immunocytochemistry-based Assay to Quantify Synapse Number’, Journal of Visualized Experiments, (45) DOI: 10.3791/2270
  61. Ishioka, N., Sato, J., Nakamura, J., Ohkubo, T., Takeda, A. and Kurioka, S. (1995) ‘In vivo modification of GABAA receptor with a high dose of pyridoxal phosphate induces tonic-clonic convulsion in immature mice.’, Neurochemistry international, 26(4), pp. 369–73. DOI: 10.1016/0197-0186(94)00145-k
  62. Item, C. B., Stöckler-Ipsiroglu, S., Stromberger, C., Mühl, A., Alessandrì, M. G., Bianchi, M. C., Tosetti, M., Fornai, F. and Cioni, G. (2001) ‘Arginine:Glycine Amidinotransferase Deficiency: The Third Inborn Error of Creatine Metabolism in Humans’, The American Journal of Human Genetics, 69(5), pp. 1127–1133. DOI: 10.1086/323765
  63. Iyer, G. S., Krahe, R., Goodwin, L. A., Doggett, N. A., Siciliano, M. J., Funanage, V. L. and Proujansky, R. (1996) ‘Identification of a testis-expressed creatine transporter gene at 16p11.2 and confirmation of the X-linked locus to Xq28.’, Genomics, 34(1), pp. 143–6 DOI: 10.1006/geno.1996.0254
  64. Joncquel-Chevalier Curt, M., Voicu, P. M., Fontaine, M., Dessein, A. F., Porchet, N., Mention-Mulliez, K., Dobbelaere, D., Soto-Ares, G., Cheillan, D. and Vamecq, J. (2015) ‘Creatine biosynthesis and transport in health and disease’, Biochimie, 119, pp. 146–165.
  65. Kaidanovich-Beilin, O., Lipina, T., Vukobradovic, I., Roder, J. and Woodgett, J. R. (2011) ‘Assessment of Social Interaction Behaviors’, Journal of Visualized Experiments, (48). DOI: 10.3791/2473
  66. Kalkman, H. O. (2012) ‘Potential opposite roles of the extracellular signal-regulated kinase (ERK) pathway in autism spectrum and bipolar disorders’, Neuroscience & Biobehavioral Reviews, 36(10), pp. 2206–2213. DOI: 10.1016/j.neubiorev.2012.07.008
  67. Kempermann, G. (2015) ‘Activity Dependency and Aging in the Regulation of Adult Neurogenesis’, Cold Spring Harbor Perspectives in Biology, 7(11), p. a018929. DOI: 10.1101/cshperspect.a018929
  68. Kopra, O., Vesa, J., von Schantz, C., Manninen, T., Minye, H., Fabritius, A.-L., Rapola, J., Diggelen, O. P. van, Saarela, J., Jalanko, A. and Peltonen, L. (2004) ‘A mouse model for Finnish variant late infantile neuronal ceroid lipofuscinosis, CLN5, reveals neuropathology associated with early aging’, Human Molecular Genetics, 13(23), pp. 2893–2906 DOI: 10.1093/hmg/ddh312
  69. Kristensen, A. S., Andersen, J., Jørgensen, T. N., Sørensen, L., Eriksen, J., Loland, C. J., Strømgaard, K. and Gether, U. (2011) ‘SLC6 neurotransmitter transporters: structure, function, and regulation.’, Pharmacological reviews, 63(3), pp. 585–640. DOI: 10.1124/pr.108.000869
  70. Kuiper, J. W., Oerlemans, F. T., Fransen, J. A. and Wieringa, B. (2008) ‘Creatine kinase B deficient neurons exhibit an increased fraction of motile mitochondria’, BMC Neuroscience, 9(1), p. 73 DOI: 10.1186/1471-2202-9-73
  71. Kurosawa, Y., DeGrauw, T. J., Lindquist, D. M., Blanco, V. M., Pyne-Geithman, G. J., Daikoku, T., Chambers, J. B., Benoit, S. C. and Clark, J. F. (2012) ‘Cyclocreatine treatment improves cognition in mice with creatine transporter deficiency’, Journal of Clinical Investigation, 122(8), pp. 2837–2846. DOI: 10.1172/JCI59373
  72. Lahiri, D. K., Sokol, D. K., Erickson, C., Ray, B., Ho, C. Y. and Maloney, B. (2013) ‘Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway’, Frontiers in Cellular Neuroscience, 7. DOI: 10.3389/fncel.2013.00094
  73. Lawler, J. M., Barnes, W. S., Wu, G., Song, W. and Demaree, S. (2002) ‘Direct Antioxidant Properties of Creatine’, Biochemical and Biophysical Research Communications, 290(1), pp. 47–52. DOI: 10.1006/bbrc.2001.6164
  74. Lee, S. W., Clemenson, G. D. and Gage, F. H. (2012) ‘New neurons in an aged brain’, Behavioural Brain Research, 227(2), pp. 497–507. DOI: 10.1016/j.bbr.2011.10.009
  75. Leuzzi, V., Alessandrì, M. G., Casarano, M., Battini, R. and Cioni, G. (2008) ‘Arginine and glycine stimulate creatine synthesis in creatine transporter 1-deficient lymphoblasts’, Analytical Biochemistry, 375(1), pp. 153–155. DOI: 10.1016/j.ab.2008.01.018
  76. Leuzzi, V., Bianchi, M. C., Tosetti, M., Carducci, C., Cerquiglini, C. A., Cioni, G. and Antonozzi, I. (2000) ‘Brain creatine depletion: guanidinoacetate methyltransferase deficiency (improving with creatine supplementation).’, Neurology, 55(9), pp. 1407–9. DOI: 10.1212/wnl.55.9.1407
  77. Leuzzi, V., Mastrangelo, M., Battini, R. and Cioni, G. (2013) ‘Inborn errors of creatine metabolism and epilepsy’, Epilepsia, 54(2), pp. 217–227. DOI: 10.1111/epi.12020
  78. Levillain, O., Marescau, B. and Deyn, P. P. de (1995) ‘Guanidino compound metabolism in rats subjected to 20% to 90% nephrectomy’, Kidney International. Elsevier, 47(2), pp. 464–472. DOI: 10.1038/KI.1995.59
  79. Li, H., Thali, R. F., Smolak, C., Gong, F., Alzamora, R., Wallimann, T., Scholz, R., Pastor-Soler, N. M., Neumann, D. and Hallows, K. R. (2010) ‘Regulation of the creatine transporter by AMP-activated protein kinase in kidney epithelial cells.’, American journal of physiology. Renal physiology. American Physiological Society, 299(1), pp. F167-77. DOI: 10.1152/ajprenal.00162.2010
  80. Lipton, J. O. and Sahin, M. (2014) ‘The Neurology of mTOR’, Neuron. Elsevier Inc., 84(2), pp. 275–291. DOI: 10.1016/j.neuron.2014.09.034
  81. Loike, J. D., Zalutsky, D. L., Kaback, E., Miranda, A. F. and Silverstein, S. C. (1988) ‘Extracellular creatine regulates creatine transport in rat and human muscle cells.’, Proceedings of the National Academy of Sciences of the United States of America, 85(3), pp. 807–11 DOI: 10.1073/pnas.85.3.807
  82. Lonetti, G., Angelucci, A., Morando, L., Boggio, E. M., Giustetto, M. and Pizzorusso, T. (2010) ‘Early Environmental Enrichment Moderates the Behavioral and Synaptic Phenotype of MeCP2 Null Mice’, Biological Psychiatry, 67(7), pp. 657–665. DOI: 10.1016/j.biopsych.2009.12.022
  83. Lunardi, G., Parodi, A., Perasso, L., Pohvozcheva, A. V., Scarrone, S., Adriano, E., Florio, T., Gandolfo, C., Cupello, A., Burov, S. V. and Balestrino, M. (2006) ‘The creatine transporter mediates the uptake of creatine by brain tissue, but not the uptake of two creatine-derived compounds’, Neuroscience, 142(4), pp. 991–997. DOI: 10.1016/j.neuroscience.2006.06.058
  84. Maccarinelli, F., Pagani, A., Cozzi, A., Codazzi, F., Di Giacomo, G., Capoccia, S., Rapino, S., Finazzi, D., Politi, L. S., Cirulli, F., Giorgio, M., Cremona, O., Grohovaz, F. and Levi, S. (2015) ‘A novel neuroferritinopathy mouse model (FTL 498InsTC) shows progressive brain iron dysregulation, morphological signs of early neurodegeneration and motor coordination deficits’, Neurobiology of Disease, 81, pp. 119–133. DOI: 10.1016/j.nbd.2014.10.023
  85. Matt, S. M. and Johnson, R. W. (2016) ‘Neuro-immune dysfunction during brain aging: new insights in microglial cell regulation’, Current Opinion in Pharmacology, 26, pp. 96–101. DOI: 10.1016/j.coph.2015.10.009
  86. Matthews, R. T., Ferrante, R. J., Klivenyi, P., Yang, L., Klein, A. M., Mueller, G., Kaddurah-Daouk, R. and Beal, M. F. (1999) ‘Creatine and Cyclocreatine Attenuate MPTP Neurotoxicity’, Experimental Neurology, 157(1), pp. 142–149. DOI: 10.1006/exnr.1999.7049
  87. McFarlane, H. G., Kusek, G. K., Yang, M., Phoenix, J. L., Bolivar, V. J. and Crawley, J. N. (2008) ‘Autism-like behavioral phenotypes in BTBR T+tf/J mice’, Genes, Brain and Behavior, 7(2), pp. 152–163. DOI: 10.1111/j.1601-183X.2007.00330.x
  88. McQuail, J. A., Frazier, C. J. and Bizon, J. L. (2015) ‘Molecular aspects of age-related cognitive decline: the role of GABA signaling’, Trends in Molecular Medicine, 21(7), pp. 450–460. DOI: 10.1016/j.molmed.2015.05.002
  89. Mercimek-Mahmutoglu, S., Connolly, M. B., Poskitt, K. J., Horvath, G. A., Lowry, N., Salomons, G. S., Casey, B., Sinclair, G., Davis, C., Jakobs, C. and Stockler-Ipsiroglu, S. (2010) ‘Treatment of intractable epilepsy in a female with SLC6A8 deficiency’, Molecular Genetics and Metabolism, 101(4), pp. 409–412. DOI: 10.1016/j.ymgme.2010.08.016
  90. Mercimek-Mahmutoglu, S., Stoeckler-Ipsiroglu, S., Adami, A., Appleton, R., Araujo, H. C., Duran, M., Ensenauer, R., Fernandez-Alvarez, E., Garcia, P., Grolik, C., Item, C. B., Leuzzi, V., Marquardt, I., Muhl, A., Saelke-Kellermann, R. A., Salomons, G. S., Schulze, A., Surtees, R., van der Knaap, M. S., Vasconcelos, R., Verhoeven, N. M., Vilarinho, L., Wilichowski, E. and Jakobs, C. (2006) ‘GAMT deficiency: Features, treatment, and outcome in an inborn error of creatine synthesis’, Neurology, 67(3), pp. 480–484. DOI: 10.1212/01.wnl.0000234852.43688.bf
  91. Moy, S. S., Nadler, J. J., Perez, A., Barbaro, R. P., Johns, J. M., Magnuson, T. R., Piven, J. and Crawley, J. N. (2004) ‘Sociability and preference for social novelty in five inbred strains: an approach to assess autistic-like behavior in mice’, Genes, Brain and Behavior, 3(5), pp. 287–302. DOI: 10.1111/j.1601-1848.2004.00076.x
  92. Nabuurs, C. I., Choe, C. U., Veltien, A., Kan, H. E., van Loon, L. J. C., Rodenburg, R. J. T., Matschke, J., Wieringa, B., Kemp, G. J., Isbrandt, D. and Heerschap, A. (2013) ‘Disturbed energy metabolism and muscular dystrophy caused by pure creatine deficiency are reversible by creatine intake’, The Journal of Physiology, 591(2), pp. 571–592. DOI: 10.1113/jphysiol.2012.241760
  93. Nash, S. R., Giros, B., Kingsmore, S. F., Rochelle, J. M., Suter, S. T., Gregor, P., Seldin, M. F. and Caron, M. G. (1994) ‘Cloning, pharmacological characterization, and genomic localization of the human creatine transporter.’, Receptors & channels, 2(2), pp. 165–74.
  94. Ndika, J. D. T., Johnston, K., Barkovich, J. A., Wirt, M. D., O’Neill, P., Betsalel, O. T., Jakobs, C. and Salomons, G. S. (2012) ‘Developmental progress and creatine restoration upon long-term creatine supplementation of a patient with arginine:glycine amidinotransferase deficiency’, Molecular Genetics and Metabolism, 106(1), pp. 48–54. DOI: 10.1016/j.ymgme.2012.01.017
  95. Nicolas, M. and Hassan, B. A. (2014) ‘Amyloid precursor protein and neural development’, Development, 141(13), pp. 2543–2548. DOI: 10.1242/dev.108712
  96. Nigro, P., Pompilio, G. and Capogrossi, M. C. (2013) ‘Cyclophilin A: a key player for human disease’, Cell Death & Disease, 4(10), pp. e888–e888. DOI: 10.1038/cddis.2013.410
  97. Nota, B., Ndika, J. D. T., van de Kamp, J. M., Kanhai, W. A., van Dooren, S. J. M., van de Wiel, M. A., Pals, G. and Salomons, G. S. (2014) ‘RNA Sequencing of Creatine Transporter (SLC6A8) Deficient Fibroblasts Reveals Impairment of the Extracellular Matrix’, Human Mutation, 35(9), pp. 1128–1135 DOI: 10.1002/humu.22609
  98. Nouioua, S., Cheillan, D., Zaouidi, S., Salomons, G. S., Amedjout, N., Kessaci, F., Bou-lahdour, N., Hamadouche, T. and Tazir, M. (2013) ‘Creatine deficiency syndrome. A treatable myopathy due to arginine–glycine amidinotransferase (AGAT) defi-ciency’, Neuromuscular Disorders, 23(8), pp. 670–674. DOI: 10.1016/j.nmd.2013.04.011
  99. O’Gorman, E., Beutner, G., Dolder, M., Koretsky, A. P., Brdiczka, D. and Wallimann, T. (1997) ‘The role of creatine kinase in inhibition of mitochondrial permeability transition’, FEBS Letters. No longer published by Elsevier, 414(2), pp. 253–257. DOI: 10.1016/S0014-5793(97)01045-4
  100. Papale, A., d’Isa, R., Menna, E., Cerovic, M., Solari, N., Hardingham, N., Cambiaghi, M., Cursi, M., Barbacid, M., Leocani, L., Fasano, S., Matteoli, M. and Brambilla, R. (2017) ‘Severe Intellectual Disability and Enhanced Gamma-Aminobutyric Acidergic Synaptogenesis in a Novel Model of Rare RASopathies’, Biological Psychiatry, 81(3), pp. 179–192. DOI: 10.1016/j.biopsych.2016.06.016
  101. Peral, M. J., Vázquez-Carretero, M. D. and Ilundain, A. A. (2010) ‘Na+/Cl−/creatine transporter activity and expression in rat brain synaptosomes’, Neuroscience, 165(1), pp. 53–60. DOI: 10.1016/j.neuroscience.2009.10.001
  102. Perasso, L., Adriano, E., Ruggeri, P., Burov, S. V., Gandolfo, C. and Balestrino, M. (2009) ‘In vivo neuroprotection by a creatine-derived compound: Phosphocreatine–Mg-complex acetate’, Brain Research, 1285, pp. 158–163. DOI: 10.1016/j.brainres.2009.06.009
  103. Perasso, L., Cupello, A., Lunardi, G. L., Principato, C., Gandolfo, C. and Balestrino, M. (2003) ‘Kinetics of creatine in blood and brain after intraperitoneal injection in the rat.’, Brain research, 974(1–2), pp. 37–42. DOI: 10.1016/s0006-8993(03)02547-2
  104. Perna, M. K., Kokenge, A. N., Miles, K. N., Udobi, K. C., Clark, J. F., Pyne-Geithman, G. J., Khuchua, Z. and Skelton, M. R. (2016) ‘Creatine transporter deficiency leads to increased whole body and cellular metabolism’, Amino Acids. Springer Vienna. DOI: 10.1007/s00726-016-2291-3
  105. Póo-Argüelles, P., Arias, A., Vilaseca, M. A., Ribes, A., Artuch, R., Sans-Fito, A., Moreno, A., Jakobs, C. and Salomons, G. (2006) ‘X-Linked creatine transporter deficiency in two patients with severe mental retardation and autism’, Journal of Inherited Metabolic Disease, 29(1), pp. 220–223. DOI: 10.1007/s10545-006-0212-4
  106. Pucilowska, J., Vithayathil, J., Pagani, M., Kelly, C., Karlo, J. C., Robol, C., Morella, I., Gozzi, A., Brambilla, R. and Landreth, G. E. (2018) ‘Pharmacological Inhibition of ERK Signaling Rescues Pathophysiology and Behavioral Phenotype Associated with 16p11.2 Chromosomal Deletion in Mice’, The Journal of Neuroscience, 38(30), pp. 6640–6652. DOI: 10.1523/JNEUROSCI.0515-17.2018
  107. Pucilowska, J., Vithayathil, J., Tavares, E. J., Kelly, C., Karlo, J. C. and Landreth, G. E. (2015) ‘The 16p11.2 Deletion Mouse Model of Autism Exhibits Altered Cortical Progenitor Proliferation and Brain Cytoarchitecture Linked to the ERK MAPK Pathway’, Journal of Neuroscience, 35(7), pp. 3190–3200. DOI: 10.1523/JNEUROSCI.4864-13.2015
  108. Puusepp, H., Kall, K., Salomons, G. S., Talvik, I., Männamaa, M., Rein, R., Jakobs, C. and Õunap, K. (2010) ‘The screening of SLC6A8 deficiency among Estonian families with X-linked mental retardation.’, Journal of inherited metabolic disease, 33 Suppl 3, pp. S5-11. DOI: 10.1007/s10545-008-1063-y
  109. Pyne-Geithman, G. J., deGrauw, T. J., Cecil, K. M., Chuck, G., Lyons, M. A., Ishida, Y. and Clark, J. F. (2004) ‘Presence of normal creatine in the muscle of a patient with a mutation in the creatine transporter: a case study.’, Molecular and cellular biochemistry, 262(1–2), pp. 35–9. DOI: 10.1023/b:mcbi.0000038213.15646.4a
  110. Rao, J. S., Kellom, M., Kim, H.-W., Rapoport, S. I. and Reese, E. A. (2012) ‘Neuroinflammation and Synaptic Loss’, Neurochemical Research, 37(5), pp. 903–910. DOI: 10.1007/s11064-012-0708-2
  111. Ratto, G. M. and Pizzorusso, T. (2006) ‘A Kinase with a Vision’, in Brain Repair. Boston, MA: Springer US, pp. 122–132. DOI: 10.1007/0-387-30128-3_7
  112. Ray, B., Long, J. M., Sokol, D. K. and Lahiri, D. K. (2011) ‘Increased Secreted Amyloid Precursor Protein-α (sAPPα) in Severe Autism: Proposal of a Specific, Anabolic Pathway and Putative Biomarker’, PLoS ONE. Edited by A. I. Bush, 6(6), p. e20405. DOI: 10.1371/journal.pone.0020405
  113. Rothwell, P. E., Fuccillo, M. V., Maxeiner, S., Hayton, S. J., Gokce, O., Lim, B. K., Fowler, S. C., Malenka, R. C. and Südhof, T. C. (2014) ‘Autism-Associated Neuroligin-3 Mutations Commonly Impair Striatal Circuits to Boost Repetitive Behaviors’, Cell, 158(1), pp. 198–212 DOI: 10.1016/j.cell.2014.04.045
  114. Russell, A. P., Ghobrial, L., Wright, C. R., Lamon, S., Brown, E. L., Kon, M., Skelton, M. R. and Snow, R. J. (2014) ‘Creatine transporter (SLC6A8) knockout mice display an increased capacity for in vitro creatine biosynthesis in skeletal muscle’, Frontiers in Physiology. Frontiers, 5, p. 314 DOI: 10.3389/fphys.2014.00314
  115. Ryan, S. M. and Nolan, Y. M. (2016) ‘Neuroinflammation negatively affects adult hippocampal neurogenesis and cognition: can exercise compensate?’, Neuroscience & Biobehavioral Reviews, 61, pp. 121–131 DOI: 10.1016/j.neubiorev.2015.12.004
  116. Salomons, G. S., van Dooren, S. J. M., Verhoeven, N. M., Cecil, K. M., Ball, W. S., Degrauw, T. J. and Jakobs, C. (2001) ‘X-Linked Creatine-Transporter Gene (SLC6A8) Defect: A New Creatine-Deficiency Syndrome’, The American Journal of Human Genetics, 68(6), pp. 1497–1500. DOI: 10.1086/320595
  117. Saunders, A., Macosko, E., Wysoker, A., Goldman, M., Krienen, F., Bien, E., Baum, M., Wang, S., Goeva, A., Nemesh, J., Kamitaki, N., Brumbaugh, S., Kulp, D. and McCarroll, S. A. (2018) ‘A Single-Cell Atlas of Cell Types, States, and Other Transcriptional Patterns from Nine Regions of the Adult Mouse Brain’, bioRxiv. Cold Spring Harbor Laboratory, p. 299081 DOI: 10.1101/299081
  118. Schiaffino, M. C., Bellini, C., Costabello, L., Caruso, U., Jakobs, C., Salomons, G. S. and Bonioli, E. (2005) ‘X-linked creatine transporter deficiency’, Neurogenetics, 6(3), pp. 165–168. DOI: 10.1007/s10048-005-0002-4
  119. Sestili, P., Martinelli, C., Colombo, E., Barbieri, E., Potenza, L., Sartini, S. and Fimognari, C. (2011) ‘Creatine as an antioxidant’, Amino Acids, 40(5), pp. 1385–1396. DOI: 10.1007/s00726-011-0875-5
  120. Shaw, A. E. and Bamburg, J. R. (2017) ‘Peptide regulation of cofilin activity in the CNS: A novel therapeutic approach for treatment of multiple neurological disorders’, Pharmacology & Therapeutics, 175, pp. 17–27. DOI: 10.1016/j.pharmthera.2017.02.031
  121. Sherwin, E., Dinan, T. G. and Cryan, J. F. (2018) ‘Recent developments in understanding the role of the gut microbiota in brain health and disease’, Annals of the New York Academy of Sciences, 1420(1), pp. 5–25 DOI: 10.1111/nyas.13416
  122. Shetty, A. K. and Turner, D. A. (1998) ‘Hippocampal interneurons expressing glutamic acid decarboxylase and calcium-binding proteins decrease with aging in Fischer 344 rats.’, The Journal of comparative neurology, 394(2), pp. 252–69.
  123. Shi, L., Argenta, A. E., Winseck, A. K. and Brunso-Bechtold, J. K. (2004) ‘Stereological quantification of GAD-67-immunoreactive neurons and boutons in the hippocampus of middle-aged and old Fischer 344 × Brown Norway rats’, Journal of Comparative Neurology, 478(3), pp. 282–291. DOI: 10.1002/cne.20303
  124. Sierra, A., Beccari, S., Diaz-Aparicio, I., Encinas, J. M., Comeau, S. and Tremblay, M.-È. (2014) ‘Surveillance, Phagocytosis, and Inflammation: How Never-Resting Microglia Influence Adult Hippocampal Neurogenesis’, Neural Plasticity, 2014, pp. 1–15 DOI: 10.1155/2014/610343
  125. Silingardi, D., Angelucci, A., De Pasquale, R., Borsotti, M., Squitieri, G., Brambilla, R., Putignano, E., Pizzorusso, T. and Berardi, N. (2011) ‘ERK pathway activation bidirectionally affects visual recognition memory and synaptic plasticity in the perirhinal cortex.’, Frontiers in behavioral neuroscience. Frontiers Media SA, 5, p. 84. DOI: 10.3389/fnbeh.2011.00084
  126. Skelton, M. R., Schaefer, T. L., Graham, D. L., deGrauw, T. J., Clark, J. F., Williams, M. T. and Vorhees, C. V. (2011) ‘Creatine Transporter (CrT; Slc6a8) Knockout Mice as a Model of Human CrT Deficiency’, PLoS ONE. Edited by E. M. C. Skoulakis. Public Library of Science, 6(1), p. e16187. DOI: 10.1371/journal.pone.0016187
  127. Stöckler, S., Hanefeld, F. and Frahm, J. (1996) ‘Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism.’, Lancet (London, England), 348(9030), pp. 789–90. DOI: 10.1016/s0140-6736(96)04116-5
  128. Stöckler, S., Holzbach, U., Hanefeld, F., Marquardt, I., Helms, G., Requart, M., Hänicke, W. and Frahm, J. (1994) ‘Creatine deficiency in the brain: a new, treatable inborn error of metabolism.’, Pediatric research, 36(3), pp. 409–413. DOI: 10.1203/00006450-199409000-00023
  129. Sullivan, P. G., Geiger, J. D., Mattson, M. P. and Scheff, S. W. (2000) ‘Dietary supplement creatine protects against traumatic brain injury.’, Annals of neurology, 48(5), pp. 723–9. DOI: 10.1111/j.1460-9568.2004.03478.x
  130. Terman, A. and Brunk, U. T. (2006) ‘Oxidative Stress, Accumulation of Biological “Garbage”, and Aging’, Antioxidants & Redox Signaling, 8(1–2), pp. 197–204. DOI: 10.1089/ars.2006.8.197
  131. Thomas, G. M. and Huganir, R. L. (2004) ‘MAPK cascade signalling and synaptic plasticity’, Nature Reviews Neuroscience, 5(3), pp. 173–183. DOI: 10.1038/nrn1346
  132. Torremans, A., Marescau, B., Possemiers, I., Van Dam, D., D’Hooge, R., Isbrandt, D. and De Deyn, P. P. (2005) ‘Biochemical and behavioural phenotyping of a mouse model for GAMT deficiency’, Journal of the Neurological Sciences, 231(1–2), pp. 49–55 DOI: 10.1016/j.jns.2004.12.014
  133. Tronche, F., Kellendonk, C., Kretz, O., Gass, P., Anlag, K., Orban, P. C., Bock, R., Klein, R. and Schütz, G. (1999) ‘Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety’, Nature Genetics, 23(1), pp. 99–103. DOI: 10.1038/12703
  134. Udobi, K. C., Kokenge, A. N., Hautman, E. R., Ullio, G., Coene, J., Williams, M. T., Vorhees, C. V., Mabondzo, A. and Skelton, M. R. (2018) ‘Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8’, Genes, Brain and Behavior, 17(6), p. e12461. DOI: 10.1111/gbb.12461
  135. van de Kamp, J. M., Jakobs, C., Gibson, K. M. and Salomons, G. S. (2013) ‘New insights into creatine transporter deficiency: the importance of recycling creatine in the brain’, Journal of Inherited Metabolic Disease, 36(1), pp. 155–156. DOI: 10.1007/s10545-012-9537-3
  136. van de Kamp, J. M., Mancini, G. M. and Salomons, G. S. (2014) ‘X-linked creatine transporter deficiency: clinical aspects and pathophysiology’, Journal of Inherited Metabolic Disease, 37(5), pp. 715–733. DOI: 10.1007/s10545-014-9713-8
  137. van de Kamp, J., Betsalel, O. T., Mercimek-Mahmutoglu, S., Abulhoul, L., Grünewald, S., Anselm, I., Azzouz, H., Bratkovic, D., de Brouwer, A., Hamel, B., Kleefstra, T., Yntema, H., Campistol, J., Vilaseca, M. A., Cheillan, D., D’Hooghe, M., Diogo, L., Garcia, P., Valongo, C., Fonseca, M., Frints, S., Wilcken, B., von der Haar, S., Meijers-Heijboer, H. E., Hofstede, F., Johnson, D., Kant, S. G., Lion-Francois, L., Pitelet, G., Longo, N., Maat-Kievit, J. A., Monteiro, J. P., Munnich, A., Muntau, A. C., Nassogne, M. C., Osaka, H., Ounap, K., Pinard, J. M., Quijano-Roy, S., Poggenburg, I., Poplawski, N., Abdul-Rahman, O., Ribes, A., Arias, A., Yaplito-Lee, J., Schulze, A., Schwartz, C. E., Schwenger, S., Soares, G., Sznajer, Y., Valayannopoulos, V., Van Esch, H., Waltz, S., Wamelink, M. M. C., Pouwels, P. J. W., Errami, A., van der Knaap, M. S., Jakobs, C., Mancini, G. M. and Salomons, G. S. (2013) ‘Phenotype and genotype in 101 males with X-linked creatine transporter deficiency’, Journal of Medical Genetics, 50(7), pp. 463–472. DOI: 10.1136/jmedgenet-2013-101658
  138. van de Kamp, J., Errami, A., Howidi, M., Anselm, I., Winter, S., Phalin-Roque, J., Osaka, H., van Dooren, S. J. M., Mancini, G. M., Steinberg, S. J. and Salomons, G. S. (2015) ‘Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1’, Clinical Genetics, 87(2), pp. 141–147. DOI: 10.1111/cge.12355
  139. van de Kamp, J., Mancini, G., Pouwels, P., Betsalel, O., van Dooren, S., de Koning, I., Steenweg, M., Jakobs, C., van der Knaap, M. and Salomons, G. (2011) ‘Clinical features and X-inactivation in females heterozygous for creatine transporter defect’, Clinical Genetics. Wiley/Blackwell (10.1111), 79(3), pp. 264–272. DOI: 10.1111/j.1399-0004.2010.01460.x
  140. van de Kap, J. M., Pouwels, P. J. W., Aarsen, F. K., ten Hoopen, L. W., Knol, D. L., de Klerk, J. B., de Coo, I. F., Huijmans, J. G. M., Jakobs, C., van der Knaap, M. S., Salomons, G. S. and Mancini, G. M. S. (2012) ‘Long-term follow-up and treatment in nine boys with X-linked creatine transporter defect.’, Journal of inherited metabolic disease. Springer, 35(1), pp. 141–9. DOI: 10.1007/s10545-011-9345-1
  141. Vanderklish, P. W. and Edelman, G. M. (2002) ‘Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons.’, Proceedings of the National Academy of Sciences of the United States of America. National Academy of Sciences, 99(3), pp. 1639–44 DOI: 10.1073/pnas.032681099
  142. Vela, J., Gutierrez, A., Vitorica, J. and Ruano, D. (2003) ‘Rat hippocampal GABAergic molecular markers are differentially affected by ageing.’, Journal of neurochemistry, 85(2), pp. 368–77. DOI: 10.1046/j.1471-4159.2003.01681.x
  143. von Bernhardi, R., Eugenín-von Bernhardi, L. and Eugenín, J. (2015) ‘Microglial cell dysregulation in brain aging and neurodegeneration’, Frontiers in Aging Neuroscience, 7, p. 124. DOI: 10.3389/fnagi.2015.00124
  144. Walker, J. B. (1979) ‘Creatine: biosynthesis, regulation, and function.’, Advances in enzymology and related areas of molecular biology, 50, pp. 177–242. DOI: 10.1002/9780470122952.ch4
  145. Wang, H.-S. and Kuo, M.-F. (2007) ‘Vitamin B6 related epilepsy during childhood.’, Chang Gung medical journal, 30(5), pp. 396–401.
  146. Woo, J. A., Zhao, X., Khan, H., Penn, C., Wang, X., Joly-Amado, A., Weeber, E., Morgan, D. and Kang, D. E. (2015) ‘Slingshot-Cofilin activation mediates mitochondrial and synaptic dysfunction via Aβ ligation to β1-integrin conformers’, Cell Death & Differentiation, 22(6), pp. 921–934. DOI: 10.1038/cdd.2015.5
  147. Wyss, M. and Kaddurah-Daouk, R. (2000) ‘Creatine and Creatinine Metabolism’, Physiological reviews, 80(3), pp. 1107–1213. DOI: 10.1016/S1286-0115(06)74505-2
  148. Xu, D., Zhu, J., Jeong, S., Li, D., Hua, X., Huang, L., Zhang, J., Luo, Y. and Xia, Q. (2018) ‘Rictor Deficiency Aggravates Hepatic Ischemia/Reperfusion Injury in Mice by Suppressing Autophagy and Regulating MAPK Signaling’, Cellular Physiology and Biochemistry, 45(6), pp. 2199–2212. DOI: 10.1159/000488165
  149. Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’Shea, D. J., Sohal, V. S., Goshen, I., Finkelstein, J., Paz, J. T., Stehfest, K., Fudim, R., Ramakrishnan, C., Huguenard, J. R., Hegemann, P. and Deisseroth, K. (2011) ‘Neocortical excitation/inhibition balance in information processing and social dysfunction’, Nature. Nature Publishing Group, 477(7363), pp. 171–178. DOI: 10.1038/nature10360
  150. Zervou, S., Whittington, H. J., Russell, A. J. and Lygate, C. A. (2016) ‘Augmentation of Creatine in the Heart.’, Mini reviews in medicinal chemistry, 16(1), pp. 19–28.
  151. Zhu, X., Lee, H., Raina, A. K., Perry, G. and Smith, M. A. (2002) ‘The Role of Mitogen-Activated Protein Kinase Pathways in Alzheimer’s Disease’, Neurosignals, 11(5), pp. 270–281. DOI: 10.1159/000067426
PDF
  • Publication Year: 2020
  • Pages: 116
  • eISBN: 978-88-5518-082-5
  • Content License: CC BY 4.0
  • © 2020 Author(s)

XML
  • Publication Year: 2020
  • eISBN: 978-88-5518-083-2
  • Content License: CC BY 4.0
  • © 2020 Author(s)

PRINT
  • Publication Year: 2020
  • Pages: 116
  • ISBN: 978-88-5518-081-8
  • Content License: CC BY 4.0
  • © 2020 Author(s)

Bibliographic Information

Book Title

New insights into creatine transporter deficiency

Book Subtitle

Identification of neuropathological and metabolic targets for treatment

Authors

Angelo Molinaro

Peer Reviewed

Number of Pages

116

Publication Year

2020

Copyright Information

© 2020 Author(s)

Content License

CC BY 4.0

Metadata License

CC0 1.0

Publisher Name

Firenze University Press

DOI

10.36253/978-88-5518-082-5

ISBN Print

978-88-5518-081-8

eISBN (pdf)

978-88-5518-082-5

eISBN (xml)

978-88-5518-083-2

Series Title

Premio Tesi di Dottorato

Series ISSN

2612-8039

Series E-ISSN

2612-8020

380

Fulltext
downloads

621

Views

Search in This Book
Export Citation
Suggested Books

1,303

Open Access Books

in the Catalogue

1,746

Book Chapters

3,161,365

Fulltext
downloads

3,987

Authors

from 820 Research Institutions

of 63 Nations

63

scientific boards

from 339 Research Institutions

of 43 Nations

1,150

Referees

from 345 Research Institutions

of 37 Nations