Enhancement of brain-type creatine kinase activity ameliorates neuronal deficits in Huntington's disease

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1832, Issue 6, 2013, Pages 742-753

  Lin, Yow Sien ^a,b   Cheng, Tzu Hao ^b   Chang, Chin Pang ^a   Chen, Hui Mei ^a   Chern, Yijuang ^a  

^a INSTITUTE OF BIOMEDICAL SCIENCES   (Taiwan)

^b NATIONAL YANG MING UNIVERSITY   (Taiwan)

Author keywords

Brain type creatine kinase; Huntington's disease; Neuritogenesis; Proteasome; Protein aggregate

Indexed keywords

CREATINE KINASE; HUNTINGTIN; PROTEASOME;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BRAIN DISEASE; CONTROLLED STUDY; HOMEOSTASIS; HUNTINGTON CHOREA; MALE; MOUSE; MUTANT; NERVE CELL; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN AGGREGATION; PROTEIN EXPRESSION;

ANIMALS; BRAIN; CREATINE KINASE, BB FORM; GENE EXPRESSION REGULATION, ENZYMOLOGIC; HUMANS; HUNTINGTON DISEASE; MALE; MICE; MICE, TRANSGENIC; NERVE TISSUE PROTEINS; NEURONS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS;

EID: 84875076339     PISSN: 09254439     EISSN: 1879260X     Source Type: Journal    
DOI: 10.1016/j.bbadis.2013.02.006     Document Type: Article

References (89)

1. Walker F.O. Huntington's Disease. Semin. Neurol. 2007, 27:143-150.
2. Davies S.W., Turmaine M., Cozens B.A., DiFiglia M., Sharp A.H., Ross C.A., Scherzinger E., Wanker E.E., Mangiarini L., Bates G.P. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997, 90:537-548.
3. DiFiglia M., Sapp E., Chase K.O., Davies S.W., Bates G.P., Vonsattel J.P., Aronin N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997, 277:1990-1993.
4. Kuwert T., Lange H.W., Langen K.J., Herzog H., Aulich A., Feinendegen L.E. Cortical and subcortical glucose consumption measured by PET in patients with Huntington's disease. Brain 1990, 113(Pt 5):1405-1423.
5. Andrews T.C., Brooks D.J. Advances in the understanding of early Huntington's disease using the functional imaging techniques of PET and SPET. Mol. Med. Today 1998, 4:532-539.
6. Butterworth J., Yates C.M., Reynolds G.P. Distribution of phosphate-activated glutaminase, succinic dehydrogenase, pyruvate dehydrogenase and gamma-glutamyl transpeptidase in post-mortem brain from Huntington's disease and agonal cases. J. Neurol. Sci. 1985, 67:161-171.
7. Browne S.E., Bowling A.C., MacGarvey U., Baik M.J., Berger S.C., Muqit M.M., Bird E.D., Beal M.F. Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Ann. Neurol. 1997, 41:646-653.
8. Gu M., Gash M.T., Mann V.M., Javoy-Agid F., Cooper J.M., Schapira A.H. Mitochondrial defect in Huntington's disease caudate nucleus. Ann. Neurol. 1996, 39:385-389.
9. Cui L., Jeong H., Borovecki F., Parkhurst C.N., Tanese N., Krainc D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 2006, 127:59-69.
10. Chou S.Y., Lee Y.C., Chen H.M., Chiang M.C., Lai H.L., Chang H.H., Wu Y.C., Sun C.N., Chien C.L., Lin Y.S., Wang S.C., Tung Y.Y., Chang C., Chern Y. CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model. J. Neurochem. 2005, 93:310-320.
11. Ju T.C., Chen H.M., Lin J.T., Chang C.P., Chang W.C., Kang J.J., Sun C.P., Tao M.H., Tu P.H., Chang C., Dickson D.W., Chern Y. Nuclear translocation of AMPK-alpha1 potentiates striatal neurodegeneration in Huntington's disease. J. Cell Biol. 2011, 194:209-227.
12. Milakovic T., Johnson G.V. Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin. J. Biol. Chem. 2005, 280:30773-30782.
13. Mochel F., Durant B., Meng X., O'Callaghan J., Yu H., Brouillet E., Wheeler V.C., Humbert S., Schiffmann R., Durr A. Early alterations of brain cellular energy homeostasis in Huntington disease models. J. Biol. Chem. 2012, 287:1361-1370.
14. Wyss M., Kaddurah-Daouk R. Creatine and creatinine metabolism. Physiol. Rev. 2000, 80:1107-1213.
15. Wallimann T. Introduction - creatine: cheap ergogenic supplement with great potential for health and disease. Subcell. Biochem. 2007, 46:1-16.
16. Aksenov M.Y., Aksenova M.V., Payne R.M., Smith C.D., Markesbery W.R., Carney J.M. The expression of creatine kinase isoenzymes in neocortex of patients with neurodegenerative disorders: Alzheimer's and Pick's disease. Exp. Neurol. 1997, 146:458-465.
17. Aksenova M.V., Aksenov M.Y., Payne R.M., Trojanowski J.Q., Schmidt M.L., Carney J.M., Butterfield D.A., Markesbery W.R. Oxidation of cytosolic proteins and expression of creatine kinase BB in frontal lobe in different neurodegenerative disorders. Dement. Geriatr. Cogn. Disord. 1999, 10:158-165.
18. Sorolla M.A., Reverter-Branchat G., Tamarit J., Ferrer I., Ros J., Cabiscol E. Proteomic and oxidative stress analysis in human brain samples of Huntington disease. Free Radic. Biol. Med. 2008, 45:667-678.
19. Perluigi M., Poon H.F., Maragos W., Pierce W.M., Klein J.B., Calabrese V., Cini C., De Marco C., Butterfield D.A. Proteomic analysis of protein expression and oxidative modification in r6/2 transgenic mice: a model of Huntington disease. Mol. Cell. Proteomics 2005, 4:1849-1861.
20. Kim J., Amante D.J., Moody J.P., Edgerly C.K., Bordiuk O.L., Smith K., Matson S.A., Matson W.R., Scherzer C.R., Rosas H.D., Hersch S.M., Ferrante R.J. Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease. Biochim. Biophys. Acta 2010, 1802:673-681.
21. Zhang S.F., Hennessey T., Yang L., Starkova N.N., Beal M.F., Starkov A.A. Impaired brain creatine kinase activity in Huntington's disease. Neurodegener. Dis. 2010, 8:194-201.
22. Lin Y.S., Chen C.M., Soong B.W., Wu Y.R., Chen H.M., Yeh W.Y., Wu D.R., Lin Y.J., Poon P.W., Cheng M.L., Wang C.H., Chern Y. Dysregulated brain creatine kinase is associated with hearing impairment in mouse models of Huntington disease. J. Clin. Invest. 2011, 121:1519-1523.
23. Beal M.F. Neuroprotective effects of creatine. Amino Acids 2011, 40:1305-1313.
24. Verbessem P., Lemiere J., Eijnde B.O., Swinnen S., Vanhees L., Van Leemputte M., Hespel P., Dom R. Creatine supplementation in Huntington's disease: a placebo-controlled pilot trial. Neurology 2003, 61:925-930.
25. Tabrizi S.J., Blamire A.M., Manners D.N., Rajagopalan B., Styles P., Schapira A.H., Warner T.T. Creatine therapy for Huntington's disease: clinical and MRS findings in a 1-year pilot study. Neurology 2003, 61:141-142.
26. Dedeoglu A., Kubilus J.K., Yang L., Ferrante K.L., Hersch S.M., Beal M.F., Ferrante R.J. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J. Neurochem. 2003, 85:1359-1367.
27. Andreassen O.A., Dedeoglu A., Ferrante R.J., Jenkins B.G., Ferrante K.L., Thomas M., Friedlich A., Browne S.E., Schilling G., Borchelt D.R., Hersch S.M., Ross C.A., Beal M.F. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol. Dis. 2001, 8:479-491.
28. Ferrante R.J., Andreassen O.A., Jenkins B.G., Dedeoglu A., Kuemmerle S., Kubilus J.K., Kaddurah-Daouk R., Hersch S.M., Beal M.F. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci. 2000, 20:4389-4397.
29. Matthews R.T., Yang L., Jenkins B.G., Ferrante R.J., Rosen B.R., Kaddurah-Daouk R., Beal M.F. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J. Neurosci. 1998, 18:156-163.
30. Mangiarini L., Sathasivam K., Seller M., Cozens B., Harper A., Hetherington C., Lawton M., Trottier Y., Lehrach H., Davies S.W., Bates G.P. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 1996, 87:493-506.
31. Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970, 227:680-685.
32. Chou S.Y., Weng J.Y., Lai H.L., Liao F., Sun S.H., Tu P.H., Dickson D.W., Chern Y. Expanded-polyglutamine huntingtin protein suppresses the secretion and production of a chemokine (CCL5/RANTES) by astrocytes. J. Neurosci. 2008, 28:3277-3290.
33. Wu C.S., Lin J.T., Chien C.L., Chang W.C., Lai H.L., Chang C.P., Chern Y. Type VI adenylyl cyclase regulates neurite extension by binding to Snapin and Snap25. Mol. Cell. Biol. 2011, 31:4874-4886.
34. Chiang M.C., Lee Y.C., Huang C.L., Chern Y. cAMP-response element-binding protein contributes to suppression of the A2A adenosine receptor promoter by mutant Huntingtin with expanded polyglutamine residues. J. Biol. Chem. 2005, 280:14331-14340.
35. Lin L., Perryman M.B., Friedman D., Roberts R., Ma T.S. Determination of the catalytic site of creatine kinase by site-directed mutagenesis. Biochim. Biophys. Acta 1994, 1206:97-104.
36. Lin J.T., Chang W.C., Chen H.M., Lai H.L., Chen C.Y., Tao M.H., Chern Y. Feedback regulation between protein kinase A and the proteasome system worsens Huntington's disease. Mol. Cell. Biol. 2013, 33:1073-1084.
37. Ehrlich M.E., Conti L., Toselli M., Taglietti L., Fiorillo E., Taglietti V., Ivkovic S., Guinea B., Tranberg A., Sipione S., Rigamonti D., Cattaneo E. ST14A cells have properties of a medium-size spiny neuron. Exp. Neurol. 2001, 167:215-226.
38. Chiang M.C., Chen H.M., Lee Y.H., Chang H.H., Wu Y.C., Soong B.W., Chen C.M., Wu Y.R., Liu C.S., Niu D.M., Wu J.Y., Chen Y.T., Chern Y. Dysregulation of C/EBPalpha by mutant Huntingtin causes the urea cycle deficiency in Huntington's disease. Hum. Mol. Genet. 2007, 16:483-498.
39. Leyssens A., Nowicky A.V., Patterson L., Crompton M., Duchen M.R. The relationship between mitochondrial state, ATP hydrolysis, [Mg2+]i and [Ca2+]i studied in isolated rat cardiomyocytes. J. Physiol. 1996, 496(Pt 1):111-128.
40. Bernstein B.W., Bamburg J.R. Actin-ATP hydrolysis is a major energy drain for neurons. J. Neurosci. 2003, 23:1-6.
41. Cattaneo E., Conti L. Generation and characterization of embryonic striatal conditionally immortalized ST14A cells. J. Neurosci. Res. 1998, 53:223-234.
42. Trettel F., Rigamonti D., Hilditch-Maguire P., Wheeler V.C., Sharp A.H., Persichetti F., Cattaneo E., MacDonald M.E. Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells. Hum. Mol. Genet. 2000, 9:2799-2809.
43. Zhao J., Schmieg F.I., Simmons D.T., Molloy G.R. Mouse p53 represses the rat brain creatine kinase gene but activates the rat muscle creatine kinase gene. Mol. Cell. Biol. 1994, 14:8483-8492.
44. Willis D., Zhang Y., Molloy G.R. Transcription of brain creatine kinase in U87-MG glioblastoma is modulated by factor AP2. Biochim. Biophys. Acta 2005, 1728:18-33.
45. Kuzhikandathil E.V., Molloy G.R. Proximal promoter of the rat brain creatine kinase gene lacks a consensus CRE element but is essential for the cAMP-mediated increased transcription in glioblastoma cells. J. Neurosci. Res. 1999, 56:371-385.
46. Shea T.B., Fischer I., Sapirstein V.S. Effect of retinoic acid on growth and morphological differentiation of mouse NB2a neuroblastoma cells in culture. Brain Res. 1985, 353:307-314.
47. Hershko A., Ciechanover A. The ubiquitin system. Annu. Rev. Biochem. 1998, 67:425-479.
48. Glickman M.H., Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol. Rev. 2002, 82:373-428.
49. Shin J.B., Streijger F., Beynon A., Peters T., Gadzala L., McMillen D., Bystrom C., Van der Zee C.E., Wallimann T., Gillespie P.G. Hair bundles are specialized for ATP delivery via creatine kinase. Neuron 2007, 53:371-386.
50. Wang J., Wang C.E., Orr A., Tydlacka S., Li S.H., Li X.J. Impaired ubiquitin-proteasome system activity in the synapses of Huntington's disease mice. J. Cell Biol. 2008, 180:1177-1189.
51. Huang C.L., Yang J.M., Wang K.C., Lee Y.C., Lin Y.L., Yang Y.C., Huang N.K. Gastrodia elata prevents huntingtin aggregations through activation of the adenosine A(2)A receptor and ubiquitin proteasome system. J. Ethnopharmacol. 2011, 138:162-168.
52. Rickardson L., Wickstrom M., Larsson R., Lovborg H. Image-based screening for the identification of novel proteasome inhibitors. J. Biomol. Screen. 2007, 12:203-210.
53. Oyler G.A., Higgins G.A., Hart R.A., Battenberg E., Billingsley M., Bloom F.E., Wilson M.C. The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations. J. Cell Biol. 1989, 109:3039-3052.
54. Ye C., Zhang Y., Wang W., Wang J., Li H. Inhibition of neurite outgrowth and promotion of cell death by cytoplasmic soluble mutant huntingtin stably transfected in mouse neuroblastoma cells. Neurosci. Lett. 2008, 442:63-68.
55. Choi H., Park C.S., Kim B.G., Cho J.W., Park J.B., Bae Y.S., Bae D.S. Creatine kinase B is a target molecule of reactive oxygen species in cervical cancer. Mol. Cells 2001, 12:412-417.
56. Mekhfi H., Veksler V., Mateo P., Maupoil V., Rochette L., Ventura-Clapier R. Creatine kinase is the main target of reactive oxygen species in cardiac myofibrils. Circ. Res. 1996, 78:1016-1027.
57. Zhao T.J., Yan Y.B., Liu Y., Zhou H.M. The generation of the oxidized form of creatine kinase is a negative regulation on muscle creatine kinase. J. Biol. Chem. 2007, 282:12022-12029.
58. Hara H., Araya J., Takasaka N., Fujii S., Kojima J., Yumino Y., Shimizu K., Ishikawa T., Numata T., Kawaishi M., Saito K., Hirano J., Odaka M., Morikawa T., Hano H., Nakayama K., Kuwano K. Involvement of creatine kinase B in cigarette smoke-induced bronchial epithelial cell senescence. Am. J. Respir. Cell Mol. Biol. 2012, 46:306-312.
59. Aksenova M.V., Aksenov M.Y., Markesbery W.R., Butterfield D.A. Aging in a dish: age-dependent changes of neuronal survival, protein oxidation, and creatine kinase BB expression in long-term hippocampal cell culture. J. Neurosci. Res. 1999, 58:308-317.
60. Bae B.I., Xu H., Igarashi S., Fujimuro M., Agrawal N., Taya Y., Hayward S.D., Moran T.H., Montell C., Ross C.A., Snyder S.H., Sawa A. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005, 47:29-41.
61. Dunah A.W., Jeong H., Griffin A., Kim Y.M., Standaert D.G., Hersch S.M., Mouradian M.M., Young A.B., Tanese N., Krainc D. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002, 296:2238-2243.
62. Steffan J.S., Kazantsev A., Spasic-Boskovic O., Greenwald M., Zhu Y.Z., Gohler H., Wanker E.E., Bates G.P., Housman D.E., Thompson L.M. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:6763-6768.
63. Wang F., Samudio I., Safe S. Transcriptional activation of rat creatine kinase B by 17beta-estradiol in MCF-7 cells involves an estrogen responsive element and GC-rich sites. J. Cell. Biochem. 2001, 84:156-172.
64. Wu-Peng X.S., Pugliese T.E., Dickerman H.W., Pentecost B.T. Delineation of sites mediating estrogen regulation of the rat creatine kinase B gene. Mol. Endocrinol. 1992, 6:231-240.
65. Wallimann T., Hemmer W. Creatine kinase in non-muscle tissues and cells. Mol. Cell. Biochem. 1994, 133-134:193-220.
66. Wallimann T., Tokarska-Schlattner M., Schlattner U. The creatine kinase system and pleiotropic effects of creatine. Amino Acids 2011, 40:1271-1296.
67. Kuiper J.W., Oerlemans F.T., Fransen J.A., Wieringa B. Creatine kinase B deficient neurons exhibit an increased fraction of motile mitochondria. BMC Neurosci. 2008, 9:73.
68. Trushina E., Dyer R.B., Badger J.D., Ure D., Eide L., Tran D.D., Vrieze B.T., Legendre-Guillemin V., McPherson P.S., Mandavilli B.S., Van Houten B., Zeitlin S., McNiven M., Aebersold R., Hayden M., Parisi J.E., Seeberg E., Dragatsis I., Doyle K., Bender A., Chacko C., McMurray C.T. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell. Biol. 2004, 24:8195-8209.
69. Chang D.T., Rintoul G.L., Pandipati S., Reynolds I.J. Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol. Dis. 2006, 22:388-400.
70. Kim J., Moody J.P., Edgerly C.K., Bordiuk O.L., Cormier K., Smith K., Beal M.F., Ferrante R.J. Mitochondrial loss, dysfunction and altered dynamics in Huntington's disease. Hum. Mol. Genet. 2010, 19:3919-3935.
71. Joshi P.R., Wu N.P., Andre V.M., Cummings D.M., Cepeda C., Joyce J.A., Carroll J.B., Leavitt B.R., Hayden M.R., Levine M.S., Bamford N.S. Age-dependent alterations of corticostriatal activity in the YAC128 mouse model of Huntington disease. J. Neurosci. 2009, 29:2414-2427.
72. Cepeda C., Hurst R.S., Calvert C.R., Hernandez-Echeagaray E., Nguyen O.K., Jocoy E., Christian L.J., Ariano M.A., Levine M.S. Transient and progressive electrophysiological alterations in the corticostriatal pathway in a mouse model of Huntington's disease. J. Neurosci. 2003, 23:961-969.
73. Laforet G.A., Sapp E., Chase K., McIntyre C., Boyce F.M., Campbell M., Cadigan B.A., Warzecki L., Tagle D.A., Reddy P.H., Cepeda C., Calvert C.R., Jokel E.S., Klapstein G.J., Ariano M.A., Levine M.S., DiFiglia M., Aronin N. Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. J. Neurosci. 2001, 21:9112-9123.
74. Usdin M.T., Shelbourne P.F., Myers R.M., Madison D.V. Impaired synaptic plasticity in mice carrying the Huntington's disease mutation. Hum. Mol. Genet. 1999, 8:839-846.
75. Phillips W., Morton A.J., Barker R.A. Abnormalities of neurogenesis in the R6/2 mouse model of Huntington's disease are attributable to the in vivo microenvironment. J. Neurosci. 2005, 25:11564-11576.
76. Liu C.W., Li X., Thompson D., Wooding K., Chang T.L., Tang Z., Yu H., Thomas P.J., DeMartino G.N. ATP binding and ATP hydrolysis play distinct roles in the function of 26S proteasome. Mol. Cell 2006, 24:39-50.
77. Smith D.M., Kafri G., Cheng Y., Ng D., Walz T., Goldberg A.L. ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins. Mol. Cell 2005, 20:687-698.
78. Yi J.J., Ehlers M.D. Ubiquitin and protein turnover in synapse function. Neuron 2005, 47:629-632.
79. Patrick G.N. Synapse formation and plasticity: recent insights from the perspective of the ubiquitin proteasome system. Curr. Opin. Neurobiol. 2006, 16:90-94.
80. Laser H., Mack T.G., Wagner D., Coleman M.P. Proteasome inhibition arrests neurite outgrowth and causes "dying-back" degeneration in primary culture. J. Neurosci. Res. 2003, 74:906-916.
81. Mahajan V.B., Pai K.S., Lau A., Cunningham D.D. Creatine kinase, an ATP-generating enzyme, is required for thrombin receptor signaling to the cytoskeleton. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:12062-12067.
82. Inoue K., Ueno S., Fukuda A. Interaction of neuron-specific K+-Cl- cotransporter, KCC2, with brain-type creatine kinase. FEBS Lett. 2004, 564:131-135.
83. Inoue K., Yamada J., Ueno S., Fukuda A. Brain-type creatine kinase activates neuron-specific K+-Cl- co-transporter KCC2. J. Neurochem. 2006, 96:598-608.
84. Salin-Cantegrel A., Shekarabi M., Holbert S., Dion P., Rochefort D., Laganiere J., Dacal S., Hince P., Karemera L., Gaspar C., Lapointe J.Y., Rouleau G.A. HMSN/ACC truncation mutations disrupt brain-type creatine kinase-dependant activation of K+/Cl- cotransporter 3. Hum. Mol. Genet. 2008.
85. Rivera C., Voipio J., Payne J.A., Ruusuvuori E., Lahtinen H., Lamsa K., Pirvola U., Saarma M., Kaila K. The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 1999, 397:251-255.
86. Gulacsi A., Lee C.R., Sik A., Viitanen T., Kaila K., Tepper J.M., Freund T.F. Cell type-specific differences in chloride-regulatory mechanisms and GABA(A) receptor-mediated inhibition in rat substantia nigra. J. Neurosci. 2003, 23:8237-8246.
87. Li H., Khirug S., Cai C., Ludwig A., Blaesse P., Kolikova J., Afzalov R., Coleman S.K., Lauri S., Airaksinen M.S., Keinanen K., Khiroug L., Saarma M., Kaila K., Rivera C. KCC2 interacts with the dendritic cytoskeleton to promote spine development. Neuron 2007, 56:1019-1033.
88. Braissant O. Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers. J. Inherit. Metab. Dis. 2012, 35:655-664.
89. Lawler J.M., Barnes W.S., Wu G., Song W., Demaree S. Direct antioxidant properties of creatine. Biochem. Biophys. Res. Commun. 2002, 290:47-52.