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Review

Impact of transporters and enzymes from blood–cerebrospinal fluid barrier and brain parenchyma on CNS drug uptake

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Pages 961-972 | Received 13 Jun 2018, Accepted 15 Aug 2018, Published online: 05 Sep 2018

References

  • Reese TS, Karnovsky MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967;34:207–217.
  • Abbott NJ, Patabendige AAK, Dolman DEM, et al. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010;37:13–25.
  • Becker NH, Novikoff AB, Zimmerman HM. Fine structure observations of the uptake of intravenously injected peroxidase by the rat choroid plexus. J Histochem Cytochem. 1967;15:160–165.
  • Nabeshima S, Reese TS, Landis DMD, et al. Junctions in the meninges and marginal glia. J Comp Neurol. 1975;164:127–169.
  • Abbott NJ, Friedman A. Overview and introduction: the blood-brain barrier in health and disease. Epilepsia. 2012;53:1–6.
  • Abbott NJ. Blood–brain barrier structure and function and the challenges for CNS drug delivery. J Inherit Metab Dis. 2013;36:437–449.
  • Abbott NJ, Pizzo ME, Preston JE, et al. The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system? Acta Neuropathol. 2018;135:387–407.
  • Abbott NJ, Romero IA. Transporting therapeutics across the blood-brain barrier. Mol Med Today. 1996;2:106–113.
  • Shawahna R, Uchida Y, Declèves X, et al. Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. Mol Pharm. 2011;8:1332–1341.
  • Uchida Y, Ohtsuki S, Katsukura Y, et al. Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors. J Neurochem. 2011;117:333–345.
  • Zeiadeh I, Najjar A, Karaman R. Strategies for enhancing the permeation of CNS-active drugs through the blood-brain barrier: a review. Molecules. 2018;23:1289.
  • Saunders NR, Daneman R, Dziegielewska KM, et al. Transporters of the blood–brain and blood–CSF interfaces in development and in the adult. Mol Aspects Med. 2013;34:742–752.
  • Farthing CA, Sweet DH. Expression and function of organic cation and anion transporters (SLC22 family) in the CNS. Curr Pharm Des. 2014;20:1472–1486.
  • Praetorius J, Damkier HH. Transport across the choroid plexus epithelium. Am J Physiol Cell Physiol. 2017;312:C673–C686.
  • Strazielle N, Ghersi-Egea J-F. Potential pathways for CNS drug delivery across the blood-cerebrospinal fluid barrier. Curr Pharm Des. 2016;22:5463–5476.
  • G-E J-F, Strazielle N, Catala M, et al. Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease. Acta Neuropathol. 2018;135:337–361.
  • Ghersi-Egea JF, Walther B, Perrin R, et al. Inducibility of rat brain drug-metabolizing enzymes. Eur J Drug Metab Pharmacokinet. 1987;12:263–265.
  • Ghersi-Egea JF, Leninger-Muller B, Suleman G, et al. Localization of drug-metabolizing enzyme activities to blood-brain interfaces and circumventricular organs. J Neurochem. 1994;62:1089–1096.
  • Declèves X, Strazielle N, Scherrmann JM, et al. Drug metabolism at the blood–brain and blood–CSF barriers. Drug delivery to the brain. New York (NY): Springer; 2014.
  • Minn A, Ghersi-Egea JF, Perrin R, et al. Drug metabolizing enzymes in the brain and cerebral microvessels. Brain Res Brain Res Rev. 1991;16:65–82.
  • Brownson E, Abbruscato T, Gillespie T, et al. Effect of peptidases at the blood brain barrier on the permeability of enkephalin. ASPET. 1994;270:675–680.
  • Strazielle N, Ghersi-Egea JF. Physiology of blood–brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm. 2013;10:1473–1491.
  • Spector R, Keep RF, Robert Snodgrass S, et al. A balanced view of choroid plexus structure and function: focus on adult humans. Exp Neurol. 2015;267:78–86.
  • Wong AD, Ye M, Levy AF, et al. The blood-brain barrier: an engineering perspective. Front Neuroeng. 2013;6:7.
  • Patel MM, Patel BM. Crossing the blood–brain barrier: recent advances in drug delivery to the brain. CNS Drugs. 2017;31:109–133.
  • Ecker G, Clausen RP, Sitte HH. Transporters as drug targets. Weinheim: Wiley; 2017.
  • Römermann K, Fedrowitz M, Hampel P, et al. Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain. Neuropharmacology. 2017;117:182–194.
  • Daood M, Tsai C, Ahdab-Barmada M, et al. ABC transporter (P-gp/ABCB1, MRP1/ABCC1, BCRP/ABCG2) expression in the developing human CNS. Neuropediatrics. 2008;39:211–218.
  • Urquhart BL, Kim RB. Blood−brain barrier transporters and response to CNS-active drugs. Eur J Clin Pharmacol. 2009;65:1063–1070.
  • Szabó K, Nagy Z, Juhász V, et al. Species specificity profiling of rat and human organic cation/carnitine transporter Slc22a5/SLC22A5 (Octn2/OCTN2). Drug Metab Pharmacokinet. 2017;32:165–171.
  • Sanchez-Covarrubias L, Slosky LM, Thompson BJ, et al. Transporters at CNS barrier sites: obstacles or opportunities for drug delivery? Curr. Pharm Des. 2014;20:1422–1449.
  • Parker MD. Mouse models of SLC4-linked disorders of HCO3– transporter dysfunction. Am J Physiol Cell Physiol. 2018;314:C569–C588.
  • Sinning A, Liebmann L, Hübner CA. Disruption of Slc4a10 augments neuronal excitability and modulates synaptic short-term plasticity. Front Cell Neurosci. 2015;9:223.
  • Gurnett CA, Veile R, Zempel J, et al. Disruption of sodium bicarbonate transporter SLC4A10 in a patient with complex partial epilepsy and mental retardation. Arch Neurol. 2008;65:550.
  • Lorenzo AV, Cutler RWP. Amino acid transport by choroid plexus in vitro. J Neurochem. 1969;16:577–585.
  • Akanuma S, Sakurai T, Tachikawa M, et al. Transporter-mediated L-glutamate elimination from cerebrospinal fluid: possible involvement of excitatory amino acid transporters expressed in ependymal cells and choroid plexus epithelial cells. Fluids Barriers CNS. 2015;12:11.
  • Leke R, Schousboe A. The glutamine transporters and their role in the glutamate/GABA–glutamine cycle. Adv Neurobiol. 2016;13:223–257.
  • Leiderman DB, Balish M, Bromfield EB, et al. Effect of valproate on human cerebral glucose metabolism. Epilepsia. 1991;32:417–422.
  • Wong HY, Chu TS, Lai JC, et al. Sodium valproate inhibits glucose transport and exacerbates Glut1-deficiency in vitro. J Cell Biochem. 2005;96:775–785.
  • Patching SG. Glucose transporters at the blood-brain barrier: function, regulation and gateways for drug delivery. Mol Neurobiol. 2017;54:1046–1077.
  • Sanchez-Covarrubias L, Slosky LM, Thompson BJ, et al. Transporters at CNS barrier sites: obstacles or opportunities for drug delivery? Curr Pharm Des. 2014;20:1422–1449.
  • Halestrap AP, The MD. SLC16 gene family? From monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch Eur J Physiol Arch Eur J Physiol. 2004;447:619–628.
  • Klepper J, Voit T. Facilitated glucose transporter protein type 1 (GLUT1) deficiency syndrome: impaired glucose transport into brain – a review. Eur J Pediatr. 2002;161:295–304.
  • Fujiyoshi M, Tachikawa M, Ohtsuki S, et al. Amyloid-β peptide(1–40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier. J Neurochem. 2011;118:407–415.
  • Yassine HN, Feng Q, Chiang J, et al. ABCA1-mediated cholesterol efflux capacity to cerebrospinal fluid is reduced in patients with mild cognitive impairment and Alzheimer’s disease. J Am Heart Assoc. 2016;5:e002886.
  • Tansley GH, Burgess BL, Bryan MT, et al. The cholesterol transporter ABCG1 modulates the subcellular distribution and proteolytic processing of β-amyloid precursor protein. J Lipid Res. 2007;48:1022–1034.
  • Matsumoto K, Chiba Y, Fujihara R, et al. Immunohistochemical analysis of transporters related to clearance of amyloid-β peptides through blood–cerebrospinal fluid barrier in human brain. Histochem Cell Biol. 2015;144:597–611.
  • Scheiber IF, Mercer JFB, Dringen R. Metabolism and functions of copper in brain. Prog Neurobiol. 2014;116:33–57.
  • Ho HTB, Dahlin A, Wang J. Expression profiling of solute carrier gene families at the blood-CSF barrier. Front. Pharmacol. 2012;3:154.
  • Begley DJ. Efflux mechanisms in the central nervous system: a powerful influence on drug distribution within the brain. New York (NY): Elsevier; 2004.
  • Flores K, Manautou JE, Renfro JL. Gender-specific expression of ATP-binding cassette (Abc) transporters and cytoprotective genes in mouse choroid plexus. Toxicology. 2017;386:84–92.
  • Soontornmalai A, Vlaming MLH, Fritschy J-M. Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood–brain barrier. Neuroscience. 2006;138:159–169.
  • Flores K, Manautou JE, Renfro JL. Gender-specific expression of ATP-binding cassette (Abc) transporters and cytoprotective genes in mouse choroid plexus. Toxicology. 2017;386:84–92.
  • Santos CRA, Duarte AC, Quintela T, et al. The choroid plexus as a sex hormone target: functional implications. Front Neuroendocrinol. 2017;44:103–121.
  • Tachikawa M, Ozeki G, Higuchi T, et al. Role of the blood-cerebrospinal fluid barrier transporter as a cerebral clearance system for prostaglandin E 2 produced in the brain. J Neurochem. 2012;123:750–760.
  • Kuroda M, Kusuhara H, Endou H, et al. Rapid elimination of cofactor from the cerebrospinal fluid is mediated by a benzylpenicillin-sensitive mechanism distinct from organic anion transporter 3. J Pharmacol Exp Ther. 2005;314:855–861.
  • Ohtsuki S, Takizawa T, Takanaga H, et al. Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells. J Neurochem. 2004;90:743–749.
  • Nagata Y, Kusuhara H, Endou H, et al. Expression and functional characterization of rat organic anion transporter 3 (rOat3) in the choroid plexus. Mol Pharmacol. 2002;61:982–988.
  • Tachikawa M, Hosoya K, Terasaki T. Pharmacological significance of prostaglandin E2 and D2 transport at the brain barriers. Adv Pharmacol. 2014;71:337–360.
  • Nagle MA, Wu W, Eraly SA, et al. Organic anion transport pathways in antiviral handling in choroid plexus in Oat1 (Slc22a6) and Oat3 (Slc22a8) deficient tissue. Neurosci Lett. 2013;534:133–138.
  • De W, Jn R, Dr S, et al. Organic anion-transporting polypeptides at the blood–brain and blood–cerebrospinal fluid barriers. Curr Top Dev Biol. 2007;80:135–170.
  • Benarroch EE. Choroid plexus–CSF system: recent developments and clinical correlations. Neurology. 2016;86:286–296.
  • Hagenbuch B, Meier PJ. The superfamily of organic anion transporting polypeptides. Biochim Biophys Acta. 2003;1609:1–18.
  • Richardson SJ, Van Herck S, Delbaere J, et al. The affinity of transthyretin for T3 or T4 does not determine which form of the hormone accumulates in the choroid plexus. Gen Comp Endocrinol. 2018;264:131–137.
  • Shen H, Smith DE, Keep RF, et al. Immunolocalization of the proton-coupled oligopeptide transporter PEPT2 in developing rat brain. Mol Pharm. 2004;1:248–256.
  • Teuscher NS, Keep RF, Smith DE. PEPT2-mediated uptake of neuropeptides in rat choroid plexus. Pharm Res. 2001;18:807–813.
  • Shen H, Smith DE, Keep RF, et al. Targeted disruption of the PEPT2 gene markedly reduces dipeptide uptake in choroid plexus. J Biol Chem. 2003;278:4786–4791.
  • Chen X, Keep RF, Liang Y, et al. Influence of peptide transporter 2 (PEPT2) on the distribution of cefadroxil in mouse brain: a microdialysis study. Biochem Pharmacol. 2017;131:89–97.
  • Kamal MA, Keep RF, Smith DE. Role and relevance of PEPT2 in drug disposition, dynamics, and toxicity. Drug Metab Pharmacokinet. 2008;23:236–242.
  • Shinohara M, Tachibana M, Kanekiyo T, et al. Role of LRP1 in the pathogenesis of Alzheimer’s disease: evidence from clinical and preclinical studies. J Lipid Res. 2017;58:1267–1281.
  • Huber RD, Gao B, M-A SP, et al. Characterization of two splice variants of human organic anion transporting polypeptide 3A1 isolated from human brain. Am J Physiol Physiol. 2007;292:C795–C806.
  • Belloni-Olivi L, Marshall C, Laal B, et al. Localization of zip1 and zip4 mRNA in the adult rat brain. J Neurosci Res. 2009;87:3221–3230.
  • Aquino M. Regulation of zinc transport in the choroid plexus. 2014;
  • Fu X, Zeng A, Zheng W, et al. Upregulation of zinc transporter 2 in the blood–CSF barrier following lead exposure. Exp Biol Med. 2014;239:202–212.
  • Brittebo EB. Metabolism-dependent binding of the heterocyclic amine Trp-P-1 in endothelial cells of choroid plexus and in large cerebral veins of cytochrome P450-induced mice. Brain Res. 1994;659:91–98.
  • Dey A, Jones JE, Nebert DW. Tissue- and cell type-specific expression of cytochrome P450 1A1 and cytochrome P450 1A2 mRNA in the mouse localized in situ hybridization. Biochem Pharmacol. 1999;58:525–537.
  • Khokhar JY An investigation of CYP2B in rat brain: regulation and role in drug and toxin response. 2012.
  • Granberg L, Ostergren A, Brandt I, et al. CYP1A1 and CYP1B1 in blood-brain interfaces: CYP1A1-dependent bioactivation of 7,12-dimethylbenz(a)anthracene in endothelial cells. Drug Metab Dispos. 2003;31:259–265.
  • Cashman JR. Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab. 2000;1:181–191.
  • Strazielle N, Ghersi-Egea JF. Demonstration of a coupled metabolism-efflux process at the choroid plexus as a mechanism of brain protection toward xenobiotics. J Neurosci. 1999;19:6275–6289.
  • Burdo J, Dargusch R, Schubert D. Distribution of the cystine/glutamate antiporter system x − c in the brain, kidney, and duodenum. J Histochem Cytochem. 2006;54:549–557.
  • Lee NY, Choi HO, Kang YS. The Acetylcholinesterase inhibitors competitively inhibited an acetyl L-carnitine transport through the blood–brain barrier. Neurochem Res. 2012;37:1499–1507.
  • Monks TJ, Ghersi-Egea JF, Philbert M, et al. Symposium overview: the role of glutathione in neuroprotection and neurotoxicity. Toxicol. Sci. 1999;51:161–177.
  • Zigova T, Sanberg PR, Sanchez-Ramos JR. Neural stem cells: methods and protocols. New York (NY): Humana Press; 2002.
  • Di L, Kerns EH. Drug-like properties: concepts, structure design and methods from ADME to toxicity optimization. Cambridge (MA): Academic Press; 2008.
  • Hough LB, Nalwalk JW, Ding X, et al. Opioid analgesia in P450 gene cluster knockout mice: a search for analgesia-relevant isoforms. Drug Metab Dispos. 2015;43:1326–1330.
  • Somjen GG. Ions in the brain: normal function, seizures, and stroke. Oxford: Oxford University Press; 2004.
  • Liu Y, He Q. The route of nanomaterials entering brain. Neurotox. Nanomater. Nanomedicine. New York (NY): Elsevier; 2017.
  • Malynn S, Campos-Torres A, Moynagh P, et al. The pro-inflammatory cytokine TNF-α regulates the activity and expression of the serotonin transporter (SERT) in astrocytes. Neurochem Res. 2013;38:694–704.
  • Dodd JR, Birch NP, Waldvogel HJ, et al. Functional and immunocytochemical characterization of the creatine transporter in rat hippocampal neurons. J Neurochem. 2010;115:684–693.
  • Lowe MTJ, Faull RLM, Christie DL, et al. Distribution of the creatine transporter throughout the human brain reveals a spectrum of creatine transporter immunoreactivity. J Comp Neurol. 2015;523:699–725.
  • Vannucci SJ, Maher F, Simpson IA. Glucose transporter proteins in brain: delivery of glucose to neurons and glia. Glia. 1997;21:2–21.
  • Morris ME, Rodriguez-Cruz V, Felmlee MA. SLC and ABC transporters: expression, localization, and species differences at the blood-brain and the blood-cerebrospinal fluid barriers. AAPS J. 2017;19:1317–1331.
  • Jurcovicova J. Glucose transport in brain – effect of inflammation. Endocr Regul. 2014;48:35–48.
  • Fishwick KJ, Rylett RJ. Insulin regulates the activity of the high-affinity choline transporter CHT. PLoS One. 2015;10:e0132934.
  • Rylett RJ, Ball MJ, Colhoun EH. Evidence for high affinity choline transport in synaptosomes prepared from hippocampus and neocortex of patients with Alzheimer’s disease. Brain Res. 1983;289:169–175.
  • Uhr M, Tontsch A, Namendorf C, et al. Polymorphisms in the drug transporter gene ABCB1 predict antidepressant treatment response in depression. Neuron. 2008;57:203–209.
  • Jäkel S, Dimou L. Glial cells and their function in the adult brain: a journey through the history of their ablation. Front Cell Neurosci. 2017;11:24.
  • Vannucci SJ. Developmental expression of GLUT1 and GLUT3 glucose transporters in tat brain. J Neurochem. 2008;62:240–246.
  • Hubbard JA, Binder DK, Hubbard JA, et al. Glutamate metabolism. Astrocytes and epilepsy. New York (NY): Elsevier; 2016.
  • Light AR, Wu Y, Hughen RW, et al. Purinergic receptors activating rapid intracellular Ca+ increases in microglia. Neuron Glia Biol. 2006;2:125–138.
  • Sperlágh B, Illes P. Purinergic modulation of microglial cell activation. Purinergic Signal. 2007;3:117–127.
  • Miksys S, Rao Y, Hoffmann E, et al. Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics. J Neurochem. 2002;82:1376–1387.
  • Buratti FM, Volpe MT, Meneguz A, et al. CYP-specific bioactivation of four organophosphorothioate pesticides by human liver microsomes. Toxicol Appl Pharmacol. 2003;186:143–154.
  • Miksys S, Tyndale RF. Nicotine induces brain CYP enzymes: relevance to Parkinson’s disease. J Neural Transm Suppl. 2006;70:177–180.
  • Strolin Benedetti M, Tipton KF, Whomsley R. Amine oxidases and monooxygenases in the in vivo metabolism of xenobiotic amines in humans: has the involvement of amine oxidases been neglected? Fundam. Clin Pharmacol. 2007;21:467–480.
  • Foti RS, Dalvie DK. Cytochrome P450 and non-cytochrome P450 oxidative metabolism: contributions to the pharmacokinetics, safety, and efficacy of xenobiotics. Drug Metab Dispos. 2016;44:1229–1245.
  • Cashman JR, Zhang J. Huamn falvin-containing monooxygenases. Annu Rev Pharmacol Toxicol. 2006;46:65–100.
  • Newton HB. Handbook of brain tumor chemotherapy, molecular therapeutics, and immunotherapy. New York (NY): Elsevier; 2005.
  • Bolognesi ML, Cavalli A, Valgimigli L, et al. Multi-target-directed drug design strategy: from a dual binding site acetylcholinesterase inhibitor to a trifunctional compound against Alzheimer’s disease. J Med Chem. 2007;50:6446–6449.
  • Castañeyra-Ruiz L, González-Marrero I, Hernández-Abad LG, et al. A distal to proximal gradient of human choroid plexus development, with antagonistic expression of Glut1 and AQP1 in mature cells vs. Calbindin PCNA Proliferative Cells Front Neuroanat. 2016;10:87.
  • Redzic Z. Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences. Fluids Barriers CNS. 2011;8:3.
  • Richardson SJ, Wijayagunaratne RC, D’Souza DG, et al. Transport of thyroid hormones via the choroid plexus into the brain: the roles of transthyretin and thyroid hormone transmembrane transporters. Front Neurosci. 2015;9:66.
  • Tachikawa M, Kasai Y, Takahashi M, et al. The blood-cerebrospinal fluid barrier is a major pathway of cerebral creatinine clearance: involvement of transporter-mediated process. J Neurochem. 2008;107:432–442.
  • Tachikawa M, Hosoya KI. Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders. Fluids Barriers CNS. 2011;8:13.
  • Uchida Y, Zhang Z, Tachikawa M, et al. Quantitative targeted absolute proteomics of rat blood-cerebrospinal fluid barrier transporters: comparison with a human specimen. J Neurochem. 2015;134:1104–1115.
  • Miyajima M, Kusuhara H, Fujishima M, et al. Organic anion transporter 3 mediates the efflux transport of an amphipathic organic anion, dehydroepiandrosterone sulfate, across the blood-brain barrier in mice. Drug Metab Dispos. 2011;39:814–819.
  • Xia L, Engel K, Zhou M, et al. Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells. Am J Physiol Renal Physiol. 2007;292:F682–F690.
  • Hosoya K, Tachikawa M. Roles of organic anion/cation transporters at the blood–brain and blood–cerebrospinal fluid barriers involving uremic toxins. Clin Exp Nephrol. 2011;15:478–485.
  • Koepsell H, Lips K, Volk C. Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res. 2007;24:1227–1251.
  • Vega-Agapito V, Almeida A, Hatzoglou M, et al. Peroxynitrite stimulates l-arginine transport system y + in glial cells. J Biol Chem. 2002;277:29753–29759.
  • Zagami CJ, O’Shea RD, Lau CL, et al. Regulation of glutamate transporters in astrocytes: evidence for a relationship between transporter expression and astrocytic phenotype. Neurotox Res. 2005;7:143–149.
  • Miyazaki I, Murakami S, Torigoe N, et al. Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice. J Neurochem. 2016;136:194–204.
  • Acker LC, Pino EN, Boyden E, et al. Large volume, behaviorally-relevant illumination for optogenetics in non-human primates. J Vis Exp. 2017;128:e56330.
  • Pasantes-Morales H, Ramos-Mandujano G, Hernández-Benítez R. Taurine enhances proliferation and promotes neuronal specification of murine and human neural stem/progenitor cells. Taurine 9. New York (NY): Springer; 2015.
  • Maliszewski-Hall AM, Stein AB, Alexander M, et al. Acute hypoglycemia results in reduced cortical neuronal injury in the developing IUGR rat. Pediatr Res. 2015;78:7–13.
  • Shang T, Uihlein AV, Van Asten J, et al. 1-Methyl-4-phenylpyridinium accumulates in cerebellar granule neurons via organic cation transporter 3. J Neurochem. 2003;85:358–367.
  • Black SAG, Rylett RJ. Choline transporter CHT regulation and function in cholinergic neurons. Cent Nerv Syst Agents Med Chem. 2012;12:114–121.
  • Sarter M, Parikh V. Choline transporters, cholinergic transmission and cognition. Nat Rev Neurosci. 2005;6:48–56.
  • Stevens BR, Vo CB. Membrane transport of neuronal nitric oxide synthase substrate l-arginine is constitutively expressed with CAT1 and 4F2hc, but not CAT2 or rBAT. J Neurochem. 2002;71:564–570.
  • Hu W, Walters WM, Xia X, et al. Neuronal glutamate transporter EAAT4 is expressed in astrocytes. Glia. 2003;44:13–25.
  • Ghersi-Egea JF, Maupoil V, Ray D, et al. Electronic spin resonance detection of superoxide and hydroxyl radicals during the reductive metabolism of drugs by rat brain preparations and isolated cerebral microvessels. Free Radic Biol Med. 1998;24:1074–1081.
  • Gazzin S, Strazielle N, Schmitt C, et al. Differential expression of the multidrug resistance-related proteins ABCb1 and ABCc1 between blood-brain interfaces. J Comp Neurol. 2008;510:497–507.
  • Smith DE, Hu Y, Shen H, et al. Distribution of glycylsarcosine and cefadroxil among cerebrospinal fluid, choroid plexus, and brain parenchyma after intracerebroventricular injection is markedly different between wild-type and pept2 null mice. J Cereb Blood Flow Metab. 2011;31:250–261.
  • Atwood CS, Scarpa RC,Huang X, et al. Characterization of copper interactions with alzheimer amyloid beta peptides: identification of an attomolar-affinity copper binding site on amyloid beta1-42. J. Neurochem. 2000;75:1219–1233.
  • Römermann K, Fedrowitz M, Hampel P, et al. Multiple blood-brain barrier transport mechanisms limit bumetanide accumulation, and therapeutic potential, in the mammalian brain. Neuropharmacology. 2017;117:182–194.
  • Ehmsen JT, Liu Y, Wang Y, et al. The astrocytic transporter SLC7A10 (Asc-1) mediates glycinergic inhibition of spinal cord motor neurons. Sci Rep. 2016;6:35592.
  • Matsuo H, Kanai Y, Tokunaga M, et al. High affinity d- and l-serine transporter Asc-1: cloning and dendritic localization in the rat cerebral and cerebellar cortices. Neurosci Lett. 2004;358:123–126.
  • Safory H, Neame S, Shulman Y, et al. The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission. EMBO Rep. 2015;16:590–598.
  • McClory H, Williams D, Sapp E, et al. Glucose transporter 3 is a rab11-dependent trafficking cargo and its transport to the cell surface is reduced in neurons of CAG140 Huntington’s disease mice. Acta Neuropathol Commun. 2014;2:179.

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