{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:07:19Z","timestamp":1791320839181,"version":"4.3.1"},"reference-count":65,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T00:00:00Z","timestamp":1574640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"MIUR","doi-asserted-by":"publisher","award":["FFABR 2017"],"award-info":[{"award-number":["FFABR 2017"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The orphan drug dantrolene (DAN) is the only therapeutic treatment for malignant hyperthermia (MH), a pharmacogenetic pathology affecting 0.2 over 10,000 people in the EU. It acts by inhibiting ryanodine receptors, which are responsible for calcium recruitment in striatal muscles and brain. Because of its involvement in calcium homeostasis, DAN has been successfully investigated for its potential as neuroprotecting small molecule in several animal models of Alzheimer\u2019s disease (AD). Nevertheless, its effects at a molecular level, namely on putative targets involved in neurodegeneration, are still scarcely known. Herein, we present a prospective study on repurposing of DAN involving, besides the well-known calcium antagonism, inhibition of monoamine oxidase B and acetylcholinesterase, cytoprotection from oxidative insult, and activation of carnitine\/acylcarnitine carrier, as concurring biological activities responsible for neuroprotection.<\/jats:p>","DOI":"10.3390\/molecules24234298","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T11:12:21Z","timestamp":1574680341000},"page":"4298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["A Prospective Repurposing of Dantrolene as a Multitarget Agent for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5891-7140","authenticated-orcid":false,"given":"Isabella","family":"Bolognino","sequence":"first","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Giangregorio","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), via Amendola 122\/O, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4198-3897","authenticated-orcid":false,"given":"Leonardo","family":"Pisani","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4570-1981","authenticated-orcid":false,"given":"Modesto","family":"de Candia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1002-5087","authenticated-orcid":false,"given":"Rosa","family":"Purgatorio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Tonazzi","sequence":"additional","affiliation":[{"name":"Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies (IBIOM), National Research Council (CNR), via Amendola 122\/O, 70126 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosimo Damiano","family":"Altomare","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-7842","authenticated-orcid":false,"given":"Saverio","family":"Cellamare","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8411-304X","authenticated-orcid":false,"given":"Marco","family":"Catto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1021\/jm00317a011","article-title":"1-[(5-arylfurfurylidene) amino]-hydantoins. A new class of muscle relaxants","volume":"10","author":"Snyder","year":"1967","journal-title":"J. Med. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13023-015-0310-1","article-title":"Malignant hyperthermia: A review","volume":"10","author":"Rosenberg","year":"2015","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1365-2044.2004.03658.x","article-title":"Dantrolene\u2014A review of its pharmacology, therapeutic use and new developments","volume":"59","author":"Krause","year":"2004","journal-title":"Anaesthesia"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31624","DOI":"10.1074\/jbc.R112.349068","article-title":"Ryanodine Receptors: Structure and Function","volume":"287","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/0006-291X(88)90613-4","article-title":"Evidence for a Ca2+ channel within the ryanodine receptor complex from cardiac sarcoplasmic reticulum","volume":"151","author":"Lai","year":"1988","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1097\/00000542-200203000-00029","article-title":"Effects of dantrolene on extracellular glutamate concentration and neuronal death in the rat hippocampal CA1 region subjected to transient ischemia","volume":"96","author":"Nakayama","year":"2002","journal-title":"Anesthesiology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1097\/00004647-200202000-00008","article-title":"Role of intracellular calcium stores in cell death from oxygen-glucose deprivation in a neuronal cell line","volume":"22","author":"Wang","year":"2002","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/bja\/aem154","article-title":"Role of dantrolene in the management of the acute toxic effects of Ecstasy (MDMA)","volume":"99","author":"Moon","year":"2007","journal-title":"Br. J. Anaesth."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"434","DOI":"10.2174\/138920110791591436","article-title":"Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage","volume":"11","author":"Song","year":"2010","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10203","DOI":"10.1523\/JNEUROSCI.2645-07.2007","article-title":"Monoamine oxidase-B mediates ecstasy-induced neurotoxic effects to adolescent rat brain mitochondria","volume":"27","author":"Alves","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nrn1883","article-title":"The therapeutic potential of monoamine oxidase inhibitors","volume":"7","author":"Youdim","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"42660","DOI":"10.1039\/C6RA00302H","article-title":"Recent developments on the structure-activity relationship studies of MAO inhibitors and their role in different neurological disorders","volume":"6","author":"Kumar","year":"2016","journal-title":"RSC Adv."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s40263-013-0097-3","article-title":"Current place of monoamine oxidase inhibitors in the treatment of depression","volume":"27","author":"Shulman","year":"2013","journal-title":"CNS Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1111\/bcp.13651","article-title":"A multiple treatment comparison meta-analysis of monoamine oxidase type B inhibitors for Parkinson\u2019s disease","volume":"84","author":"Binde","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.coph.2017.04.003","article-title":"Emerging role of monoamine oxidase as a therapeutic target for cardiovascular disease","volume":"33","author":"Deshwal","year":"2017","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1007\/s00702-018-1942-9","article-title":"Monoamine oxidase inhibitors, and iron chelators in depressive illness and neurodegenerative diseases","volume":"125","author":"Youdim","year":"2018","journal-title":"J. Neural Transm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2113","DOI":"10.4155\/fmc-2016-0103","article-title":"Recent progress in repositioning Alzheimer\u2019s disease drugs based on a multitarget strategy","volume":"8","author":"Santos","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ejmech.2018.12.066","article-title":"Recent applications of hydantoin and thiohydantoin in medicinal chemistry","volume":"164","author":"Cho","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1021\/ml200196p","article-title":"Molecular insights into human monoamine oxidase B inhibition by the glitazone anti-diabetes drugs","volume":"3","author":"Binda","year":"2011","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"264","DOI":"10.2174\/1568026619666190128125912","article-title":"Target enzyme in Alzheimer\u2019s disease: Acetylcholinesterase inhibitors","volume":"19","author":"Saxena","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1021\/acschemneuro.8b00391","article-title":"Reconsideration of anticholinesterase therapeutic strategies against Alzheimer\u2019s disease","volume":"10","author":"Wang","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"811","DOI":"10.4155\/fmc-2017-0036","article-title":"Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer\u2019s disease","volume":"9","author":"Knez","year":"2017","journal-title":"Future Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4568","DOI":"10.2174\/092986711797379302","article-title":"Targeting monoamine oxidases with multipotent ligands: An emerging strategy in the search of new drugs against neurodegenerative diseases","volume":"18","author":"Pisani","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"40354","DOI":"10.1074\/jbc.M600876200","article-title":"Identification of cysteines involved in S-nitrosylation, S-glutathionylation, and oxidation to disulfides in ryanodine receptor type 1","volume":"281","author":"Goonasekera","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cmet.2015.05.014","article-title":"Acetyl coenzyme A: A central metabolite and second messenger","volume":"21","author":"Pietrocola","year":"2015","journal-title":"Cell Metab."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.mam.2011.10.008","article-title":"The mitochondrial carnitine\/acylcarnitine carrier: Function, structure and physiopathology","volume":"32","author":"Indiveri","year":"2011","journal-title":"Mol. Asp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.cmet.2012.04.005","article-title":"Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility","volume":"15","author":"Muoio","year":"2012","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1006\/phrs.2001.0890","article-title":"In vitro antioxidant properties of dantrolene sodium","volume":"44","author":"Oktay","year":"2001","journal-title":"Pharmacol. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.ejmech.2018.10.016","article-title":"Investigating alkyl nitrates as nitric oxide releasing precursors of multitarget acetylcholinesterase-monoamine oxidase B inhibitors","volume":"161","author":"Pisani","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/cmdc.201700282","article-title":"Discovery of potent dual binding site acetylcholinesterase inhibitors via homo- and heterodimerization of coumarin-based moieties","volume":"12","author":"Pisani","year":"2017","journal-title":"ChemMedChem"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1146\/annurev-biochem-061516-045115","article-title":"Protein misfolding, amyloid formation, and human disease: A summary of progress over the last decade","volume":"86","author":"Chiti","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s10571-017-0574-1","article-title":"Tau proteins and tauopathies in Alzheimer\u2019s disease","volume":"38","author":"Chong","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4810","DOI":"10.1016\/j.bmc.2008.03.052","article-title":"Design, synthesis, and biological evaluation of glycine-based molecular tongs as inhibitors of Abeta1-40 aggregation in vitro","volume":"16","author":"Cellamare","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dammers, C., Yolcu, D., Kukuk, L., Willbold, D., Pickhardt, M., Mandelkow, E., Horn, A.H.C., Heinrich Sticht, H., Malhis, M.N., and Will, N. (2016). Selection and characterization of Tau binding D-enantiomeric peptides with potential for therapy of Alzheimer disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167432"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.ejps.2017.08.004","article-title":"Mannich base approach to 5-methoxyisatin 3-(4-isopropylphenyl)hydrazone: A water-soluble prodrug for a multitarget inhibition of cholinesterases, beta-amyloid fibrillization and oligomer-induced cytotoxicity","volume":"109","author":"Pisani","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1002\/pro.87","article-title":"9,10-Anthraquinone hinders beta-aggregation: How does a small molecule interfere with Abeta-peptide amyloid fibrillation?","volume":"18","author":"Convertino","year":"2009","journal-title":"Protein Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jep.2012.12.041","article-title":"Anti-inflammatory, antimicrobial and antioxidant activities of Diospyros bipindensis (G\u00fcrke) extracts and its main constituents","volume":"146","author":"Cesari","year":"2013","journal-title":"J. Ethnopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1007\/s12640-019-0001-0","article-title":"Dopamine cytotoxicity on SH-SY5Y cells: Involvement of \u03b1-synuclein and relevance in the neurodegeneration of sporadic Parkinson\u2019s disease","volume":"35","author":"Ganguly","year":"2019","journal-title":"Neurotox. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1111\/j.1471-4159.1983.tb08123.x","article-title":"The metabolism of dopamine by both forms of monoamine oxidase in the rat brain and its inhibition by cimoxatone","volume":"40","author":"Fowler","year":"1983","journal-title":"J. Neurochem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/j.1527-3458.2002.tb00229.x","article-title":"Moclobemide: Evolution, pharmacodynamic, and pharmacokinetic properties","volume":"8","author":"Bonnet","year":"2002","journal-title":"CNS Drug Rev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5299","DOI":"10.1016\/j.bbagen.2013.08.003","article-title":"Glutathione controls the redox state of the mitochondrial carnitine\/acylcarnitine carrier Cys residues by glutathionylation","volume":"1830","author":"Giangregorio","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.bbabio.2017.04.002","article-title":"Nitric oxide inhibits the mitochondrial carnitine\/acylcarnitine carrier through reversible S-nitrosylation of cysteine 136","volume":"1858","author":"Tonazzi","year":"2017","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.bbagen.2015.10.005","article-title":"The mitochondrial carnitine\/acylcarnitine carrier is regulated by hydrogen sulfide via interaction with C136 and C155","volume":"1860","author":"Giangregorio","year":"2016","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.cbi.2013.01.006","article-title":"Inhibition of mitochondrial carnitine\/acylcarnitine transporter by H2O2: Molecular mechanism and possible implication in pathophysiology","volume":"203","author":"Tonazzi","year":"2013","journal-title":"Chem. Biol. Interact."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1097\/00000542-198310000-00002","article-title":"Dantrolene dose response in awake man: Implications for management of malignant hyperthermia","volume":"59","author":"Flewellen","year":"1983","journal-title":"Anesthesiology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"13810","DOI":"10.1074\/jbc.M006104200","article-title":"Dantrolene inhibition of ryanodine receptor Ca2+ release channels: Molecular mechanism and isoform selectivity","volume":"276","author":"Zhao","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1046\/j.1471-4159.2001.00621.x","article-title":"Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier","volume":"79","author":"Kido","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.neuroscience.2008.10.041","article-title":"Acetyl-l-carnitine provides effective in vivo neuroprotection","volume":"158","author":"Alves","year":"2009","journal-title":"Neuroscience"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.mam.2004.06.003","article-title":"Role of carnitine esters in brain neuropathology","volume":"25","author":"Virmani","year":"2004","journal-title":"Mol. Aspects Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.pharmthera.2008.08.008","article-title":"Carnitine in metabolic disease: Potential for pharmacological intervention","volume":"120","author":"Arduini","year":"2008","journal-title":"Pharmacol. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.ejmech.2019.05.062","article-title":"Investigating 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole as scaffold of butyrylcholinesterase-selective inhibitors with additional neuroprotective activities for Alzheimer\u2019s disease","volume":"177","author":"Purgatorio","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.abb.2014.07.015","article-title":"Investigation on the influence of (Z)-3-(2-(3-chlorophenyl)hydrazono)-5,6-dihydroxyindolin-2-one (PT2) on \u03b2-amyloid(1\u201340) aggregation and toxicity","volume":"560","author":"Catto","year":"2014","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1038\/nprot.2009.151","article-title":"Isolation of mitochondria-associated membranes and mitochondria from animal tissues and cells","volume":"4","author":"Wieckowski","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1042\/bj1860177","article-title":"A simple and fast method for the isolation of basolateral plasma membranes from rat small-intestinal epithelial cells","volume":"186","author":"Scalera","year":"1980","journal-title":"Biochem. J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1073\/pnas.72.3.883","article-title":"A mitochondrial carnitine acylcarnitine translocase system","volume":"72","author":"Pande","year":"1975","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0076-6879(95)60150-3","article-title":"Mitochondrial metabolite carrier proteins: Purification, reconstitution, and transport studies","volume":"260","author":"Palmieri","year":"1995","journal-title":"Meth. Enzymol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1006\/bbrc.1998.9197","article-title":"Bacterial overexpression, purification, and reconstitution of the carnitine\/acylcarnitine carrier from rat liver mitochondria","volume":"249","author":"Indiveri","year":"1998","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0378-1119(89)90358-2","article-title":"Site-directed mutagenesis by overlap extension using the polymerase chain reaction","volume":"77","author":"Ho","year":"1989","journal-title":"Gene"},{"key":"ref_60","unstructured":"(2019, October 23). EC50 Calculator. Available online: https:\/\/www.aatbio.com\/tools\/ec50-calculator\/."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.3389\/fphys.2018.01520","article-title":"Repurposing proteostasis-modifying drugs to prevent or treat age-related dementia: A systematic review","volume":"9","author":"Heard","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.omtn.2018.02.002","article-title":"Repurposing dantrolene for long-term combination therapy to potentiate antisense-mediated DMD exon skipping in the mdx mouse","volume":"11","author":"Wang","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1196\/annals.1320.003","article-title":"Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism","volume":"1033","author":"Rebouche","year":"2004","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10153","DOI":"10.1074\/jbc.M116.743070","article-title":"Amyloid \u03b2 production is regulated by \u03b22-adrenergic signaling-mediated post-translational modifications of the ryanodine receptor","volume":"292","author":"Bussiere","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1016\/j.bbrc.2016.09.053","article-title":"Dysregulation of neuronal calcium homeostasis in Alzheimer\u2019s disease\u2014A therapeutic opportunity?","volume":"483","author":"Popugaeva","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/23\/4298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:37:24Z","timestamp":1760189844000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/23\/4298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,25]]},"references-count":65,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["molecules24234298"],"URL":"https:\/\/doi.org\/10.3390\/molecules24234298","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,25]]}}}