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NCBI homepage Show account info Choline has many physiological functions throughout the body that are dependent on its available local supply. However, since choline is a charged hydrophilic cation, transport mechanisms are required for it to cross biological membranes. Choline transport is required for cellular membrane construction and is the rate-limiting step for acetylcholine production. Transport mechanisms include: (1) sodium-dependent high-affinity uptake mechanism in synaptosomes, (2) sodium-independent low-affinity mechanism on cellular membranes, and (3) unique choline uptake mechanisms (e.g., blood-brain barrier choline transport). A comprehensive overview of choline transport studies is provided. This review article examines landmark and current choline transport studies, molecular mapping, and molecular identification of these carriers. Information regarding the choline-binding site is presented by reviewing choline structural analog (hemicholinium-3 and 15, and other nitrogen/methyl-hydroxyl compounds) inhibition studies. Choline transport in Alzheimer's disease, brain ischemic events, and aging is also discussed. Emphasis throughout the article is placed on targeting the choline transporter in disease and use of this carrier as a drug delivery vector. Ferguson SS, Collier B. Ferguson SS, et al. J Neurochem. 1994 Apr;62(4):1449-57. doi: 10.1046/j.1471-4159.1994.62041449.x. J Neurochem. 1994. PMID: 8133274 Ferguson SS, Rylett RJ, Collier B. Ferguson SS, et al. J Neurochem. 1994 Oct;63(4):1328-37. doi: 10.1046/j.1471-4159.1994.63041328.x. J Neurochem. 1994. PMID: 7931285 Rylett RJ, Davis W, Walters SA. Rylett RJ, et al. Brain Res. 1993 Oct 29;626(1-2):184-9. doi: 10.1016/0006-8993(93)90578-b. Brain Res. 1993. PMID: 8281429 Michel V, Yuan Z, Ramsubir S, Bakovic M. Michel V, et al. Exp Biol Med (Maywood). 2006 May;231(5):490-504. doi: 10.1177/153537020623100503. Exp Biol Med (Maywood). 2006. PMID: 16636297 Review. Allen DD, Lockman PR. Allen DD, et al. Life Sci. 2003 Aug 15;73(13):1609-15. doi: 10.1016/s0024-3205(03)00504-6. Life Sci. 2003. PMID: 12875893 Review. Bell T, Lindner M, Langdon A, Mullins PG, Christakou A. Bell T, et al. J Neurosci. 2019 Jul 17;39(29):5740-5749. doi: 10.1523/JNEUROSCI.2110-18.2019. Epub 2019 May 20. J Neurosci. 2019. PMID: 31109959 Free PMC article. Shipkowski KA, Sanders JM, McDonald JD, Garner CE, Doyle-Eisele M, Wegerski CJ, Waidyanatha S. Shipkowski KA, et al. Toxicol Appl Pharmacol. 2019 Sep 1;378:114592. doi: 10.1016/j.taap.2019.05.011. Epub 2019 May 14. Toxicol Appl Pharmacol. 2019. PMID: 31100288 Free PMC article. Bernhard W, Lange R, Graepler-Mainka U, Engel C, Machann J, Hund V, Shunova A, Hector A, Riethmüller J. Bernhard W, et al. Nutrients. 2019 Mar 18;11(3):656. doi: 10.3390/nu11030656. Nutrients. 2019. PMID: 30889905 Free PMC article. Bernhard W, Böckmann K, Maas C, Mathes M, Hövelmann J, Shunova A, Hund V, Schleicher E, Poets CF, Franz AR. Bernhard W, et al. Eur J Nutr. 2020 Mar;59(2):729-739. doi: 10.1007/s00394-019-01940-7. Epub 2019 Mar 11. Eur J Nutr. 2020. PMID: 30859363 Wu D, Qin M, Xu D, Wang L, Liu C, Ren J, Zhou G, Chen C, Yang F, Li Y, Zhao Y, Huang R, Pourtaheri S, Kang C, Kamata M, Chen ISY, He Z, Wen J, Chen W, Lu Y. Wu D, et al. Adv Mater. 2019 May;31(18):e1807557. doi: 10.1002/adma.201807557. Epub 2019 Feb 25. Adv Mater. 2019. PMID: 30803073 Free PMC article.