Submit
Search
Submit
Menu

  • Information

  • References

  • Contents

  • [1]JW Pettegrew, WE Klunk, K Panchalingam, JN Kanfer, RJ McClure: Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer’s disease. Neurobiol Aging 16(1), 1-4 (1995)

  • [2]JW Pettegrew, J Levine, RJ McClure: Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer’s disease and geriatric depression. Mol Psychiatry 5(6), 616-632 (2000)

  • [3]HM Abdul, V Calabrese, M Calvani, DA Butterfield: Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity: implications for Alzheimer’s disease. J Neurosci Res 84(2), 398-408 (2006)

  • [4]LL Jones, DA McDonald, PR Borum: Acylcarnitines: role in brain. Prog Lipid Res 49, 61-75 (2010)

  • [5]G Traina: Update on critical evidence for use of carnitine analogs in clinical practice in CNS disorders. Nutr Diet Suppl3, 77-87 (2011)

  • [6]C Nasca, D Xenos, Y Barone, A Caruso, S Scaccianoce, F Matrisciano, G Battaglia, AA Mathé, A Pittaluga, L Lionetto, M Simmaco, F Nicoletti: L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci U S A 110(12), 4804-4809 (2013)

  • [7]L Ratnakumari, IA Qureshi, D Maysinger, RF Butterworth: Developmental deficiency of the cholinergic system in congenitally hyperammonemic spf mice: effect of acetyl-L-carnitine. J Pharmacol Exp Ther 274(1), 437-443 (1995)

  • [8]M Malaguarnera, MP Gargante, E Cristaldi, V Colonna, M Messano, A Koverech, S Neri, M Vacante, L Cammalleri, M Motta: Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Arch Gerontol Geriatr 46(2), 181-190 (2008)

  • [9]A Wawrzenczyk, KA Nalecz, MJ Nalecz: Effect of externally added carnitine on the synthesis of acetylcholine in rat cerebral cortex cells. Neurochem Int 26(6), 635-641 (1995)

  • [10]S Falchetto, G Kato, L Provini: The action of carnitines on cortical neurons. Can J Physiol Pharmacol 49(1), 1-7 (1971)

  • [11]S Ando, T Tadenuma, Y Tanaka, F Fukui, S Kobayashi, Y Ohashi, T Kawabata: Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats. J Neurosci Res 66(2), 266-271 (2001)

  • [12]H Sershen, LG. Harsing, Jr, M Banay-Schwartz, A Hashim, MT Ramacci, A Lajtha: Effect of acetyl-L-carnitine on the dopaminergic system in aging brain. J Neurosci Res 30(3), 555-559 (1991)

  • [13]A Imperato, MT Ramacci, L Angelucci: Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely mo ving rats. Neurosci Lett 107(1-3), 251-255 (1989)

  • [14]L Janiri, M Falcone, A Persico, E Tempesta: Activity of L-carnitine and L-acetylcarnitine on cholinoceptive neocortical neurons of the rat in vivo. J Neural Transm Gen Sect 86(2), 135-146 (1991)

  • [15]MA McDaniel, SF Maier, GO Einstein: “Brain-specific” nutrients: a memory cure? Nutrition 19(11-12), 957-975 (2003)

  • [16]B Smeland, TW Meisingset, K Borges, U Sonnewald: Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. Neurochem Int 61(1), 100-107 (2012)

  • [17]E Tempesta, L Janiri, C Pirrongelli: Stereospecific effects of acetylcarnitine on the spontaneous activity of brainstem neurones and their responses to acetylcholine and serotonin. Neuropharmacology 24(1), 43-50 (1985)

  • [18]A Steiber, J Kerner, CL Hoppel: Carnitine: a nutritional, biosynthetic, and functional perspective. Mol Aspects Med 25(5-6), 455-473 (2004)

  • [19]LL Bieber: Carnitine. Annu Rev Biochem 57, 261-283 (1988)

  • [20]MC Cave, RT Hurt, TH Frazier, PJ Matheson, RN Garrison, CJ McClain, SA McClave: Obesity, inflammation, and the potential application of pharmaconutrition. Nutr Clin Pract 23(1), 16-34 (2008)

  • [21]BS Kendler: Carnitine: an overview of its role in preventive medicine. Prev Med 15(4), 373-390 (1986)

  • [22]CA Stanley: Carnitine deficiency disorders in children. Ann N Y Acad Sci 1033, 42-51 (2004)

  • [23]G Goodridge, DW Back, SB Wilson, MJ Goldman: Regulation of genes for enzymes involved in fatty acid synthesis. Ann N Y Acad Sci 478, 46-62 (1986)

  • [24]KE Bloch: Sterol structure and membrane function. CRC Crit Rev Biochem 14(1), 47-92 (1983)

  • [25]Y Kido, I Tamai, A Ohnari, Y Sai, T Kagami, J Nezu, H Nikaido, N Hashimoto, M Asano, A Tsuji: Functional relevance of carnitine transporter OCTN2 to brain distribution of L-carnitine and acetyl-L-carnitine across the blood-brain barrier. J Neurochem 79(5), 959-969 (2001)

  • [26]T Nakanishi, T Hatanaka, W Huang, PD Prasad, FH Leibach, ME Ganapathy, V Ganapathy: Na+-and Cl--coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. J Physiol 532(Pt 2), 297-304 (2001)

  • [27]JL Sloan, S Mager: Cloning and functional expression of a human Na(+) and Cl(-)-dependent neutral and cationic amino acid transporter B(0+). J Biol Chem 274(34), 23740-23745 (1999)

  • [28]D Miecz, E Januszewicz, M Czeredys, BT Hinton, V Berezowski, R Cecchelli, KA Nalecz: Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood-brain barrier. J Neurochem 104(1), 113-123 (2008)

  • [29]G Traina, G Federighi, M Brunelli, R Scuri: Cytoprotective effect of acetyl-L-carnitine evidenced by analysis of gene expression in the rat brain. Mol Neurobiol 39(2), 101-106 (2009)

  • [30]V Pesce, L Nicassio, F Fracasso, C Musicco, P Cantatore, MN Gadaleta: Acetyl-L-carnitine activates the peroxisome proliferator-activated receptor-γ coactivators PGC-1α/PGC-1β-dependent signaling cascade of mitochondrial biogenesis and decreases the oxidized peroxiredoxins content in old rat liver. Rejuvenation Res 15(2), 136-139 (2012)

  • [31]MA Virmani, R Biselli, A Spadoni, S Rossi, N Corsico, M Calvani, A Fattorossi, C De Simone, E Arrigoni-Martelli: Protective actions of L-carnitine and acetyl-L-carnitine on the neurotoxicity evoked by mitochondrial uncoupling or inhibitors. Pharmacol Res 32(6), 383-389 (1995)

  • [32]MA Virmani, V Caso, A Spadoni, S Rossi, F Russo, F Gaetani: The action of acetyl-L-carnitine on the neurotoxicity evoked by amyloid fragments and peroxide on primary rat cortical neurones. Ann N Y Acad Sci 939, 162-178 (2001)

  • [33]J Liu, BN Ames: Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer’s disease, and Parkinson’s disease. Nutr Neurosci 8(2), 67-89 (2005)

  • [34]ZS Altun, D Güneş, S Aktaş, Z Erbayraktar, N Olgun: Protective effects of acetyl-L-carnitine on cisplatin cytotoxicity and oxidative stress in neuroblastoma. Neurochem Res 35(3):437-443 (2010)

  • [35]Z Altun, Y Olgun, P Ercetin, S Aktas, G Kirkim, B Serbetcioglu, N Olgun, E A Guneri: Protective effect of acetyl-l-carnitine against cisplatin ototoxicity: role of apoptosis-related genes and pro-inflammatory cytokines. Cell Prolif 47(1), 72-80 (2014)

  • [36]ML Schinetti, D Rossini, R Greco, A Bertelli: Protective action of acetylcarnitine on NADPH-induced lipid peroxidation of cardiac microsomes. Drugs Exp Clin Res 13(8), 509-515 (1987)

  • [37]J Liu, E Head, H Kuratsune, CW Cotman, BN Ames: Comparison of the effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and oxidative stress biomarkers in the brain of old rats. Ann N Y Acad Sci 1033, 117-131 (2004)

  • [38]HF Poon, V Calabrese, M Calvani, DA Butterfield: Proteomics analyses of specific protein oxidation and protein expression in aged rat brain and its modulation by L-acetylcarnitine: insights into the mechanisms of action of this proposed therapeutic agent for CNS disorders associated with oxidative. Antioxid Redox Signal 8(3-4), 381-394 (2006)

  • [39]V Calabrese, AM Giuffrida Stella, M Calvani, DA Butterfield: Acetylcarnitine and cellular stress response: roles in nutritional redox homeostasis and regulation of longevity genes. J Nutr Biochem 17(2), 73-88 (2006)

  • [40]HM Abdul, DA Butterfield: Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: implications for Alzheimer’s disease. Free Radic Biol Med 42(3), 371-384 (2007)

  • [41]S Lowitt, JI Malone, AF Salem, J Korthals, S Benford: Acetyl-L-carnitine corrects the altered peripheral nerve function of experimental diabetes. Metabolism 44(5), 677-680 (1995)

  • [42]A Pascale, S Milano, N Corsico, L Lucchi, F Battaini, EA Martelli, M Trabucchi, S Govoni: Protein kinase C activation and anti-amnesic effect of acetyl-L-carnitine.: in vitro and in vivo studies. Eur J Pharmacol 265(1-2), 1-7 (1994)

  • [43]W Shen, K. Liu, C Tian, L Yang, X Li, J Ren, L Packer, E Head, E Sharman, J Liu: Protective effects of R-alpha-lipoic acid and acetyl-L-carnitine in MIN6 and isolated rat islet cells chronically exposed to oleic acid. J Cell Biochem 104(4), 1232-1243 (2008)

  • [44]EJ Lesnefsky: Reversal of mitochondrial defects before ischemia protects the aged heart. FASEB J 20, 1543-1545 (2006)

  • [45]V Calabrese, A Ravagna, C Colombrita, G Scapagnini, E Guagliano, M Calvani, D A Butterfield, A M Giuffrida Stella: Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: involvement of the transcription factor Nrf2. J Neurosci Res 79(4), 509-521 (2005)

  • [46]SA Zanelli, NJ Solenski, RE Rosenthal, G Fiskum: Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann N Y Acad Sci 1053, 153-161 (2005)

  • [47]BK Winter, G Fiskum, LL Gallo: Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. Br J Cancer 72(5), 1173-1179 (1995)

  • [48]K Barhwal, SB Singh, SK Hota, K Jayalakshmi, G Ilavazhagan: Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats. Eur J Pharmacol 570(1-3), 97-107 (2007)

  • [49]K Barhwal, SK Hota, D Prasad, SB Singh, G Ilavazhagan: Hypoxia-induced deactivation of NGF-mediated ERK1/2 signaling in hippocampal cells neuroprotection by acetyl-L-carnitine. J Neurosci Res 86(12), 2705-2721 (2008)

  • [50]V Calabrese, M Calvani, DA Butterfield: Increased formation of short-chain organic acids after chronic ethanol administration and its interaction with the carnitine pool in rat. Arch Biochem Biophys 431(2), 271-278 (2004)

  • [51]V Calabrese, DA Butterfield, G Scapagnini, AM Stella, MD Maines: Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: relevance to brain aging, neurodegenerative disorders, and longevity. Antioxid Redox Signal 8(3-4), 444-477 (2006)

  • [52]V Calabrese, G Pennisi, M Calvani, DA Butterfield, C Mancuso, AM Giuffrida Stella. Heme Oxygenase as a Therapeutic Funnel in Nutritional Redox Homeostasis and Cellular Stress Response. In: Heat Shock Proteins in Neural Cells. Ed: CRichter-Landsberg, Springer New York, New York, NY, 39-52 (2009)

  • [53]V Calabrese, C Cornelius, C Mancuso, G Pennisi, S Calafato, F Bellia, TE Bates, AM Giuffrida Stella, T Schapira, AT Dinkova Kostova, E Rizzarelli: Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res 33(12), 2444-2471 (2008)

  • [54]K Itoh, N Wakabayashi, Y Katoh, T Ishii, K Igarashi, JD Engel, M Yamamoto: Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev 13(1), 76-86 (1999)

  • [55]V Calabrese, C Colombrita, E Guagliano, M Sapienza, A Ravagna, V Cardile, G Scapagnini, AM Santoro, A Mangiameli, DA Butterfield, AM Giuffrida Stella, E Rizzarelli: Protective effect of carnosine during nitrosative stress in astroglial cell cultures. Neurochem Res 30(6-7), 797-807 (2005)

  • [56]A Virmani, L Pinto, Z Binienda, S Ali: Food, nutrigenomics, and neurodegeneration--neuroprotection by what you eat! Mol Neurobiol 48(2), 353-362 (2013)

  • [57]A Kravets, Z Hu, T Miralem, MD Torno, MD Maines: Biliverdin reductase, a novel regulator for induction of activating transcription factor-2 and heme oxygenase-1. J Biol Chem 279, 19916-19923 (2004)

  • [58]CSõti, E Nagy, Z Giricz, L Vígh, P Csermely, P Ferdinandy: Heat shock proteins as emerging therapeutic targets. Br J Pharmacol 146(6), 769-780 (2005)

  • [59]JR Glover, S Lindquist: Hsp104, Hsp70, and Hsp40. Cell 94, 73-82 (1998)

  • [60]G Traina, S Valleggi, R Bernardi, M Rizzo, M Calvani, R Nicolai, L Mosconi, M Durante, M Brunelli: Identification of differentially expressed genes induced in the rat brain by acetyl-L-carnitine as evidenced by suppression subtractive hybridisation. Brain Res Mol Brain Res 132(1), 57-63 (2004)

  • [61]T Furuno, T Kanno, K Arita, M Asami, T Utsumi, Y Doi, M Inoue, K Utsumi: Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition. Biochem Pharmacol 62(8), 1037-1046 (2001)

  • [62]T Ishii, Y Shimpo, Y Matsuoka, K Kinoshita: Anti-apoptotic effect of acetyl-L-carnitine and L-carnitine in primary cultured neurons. Jpn J Pharmacol 83(2), 119-124 (2000)

  • [63]EArrigoni-Martelli, V Caso: Carnitine protects mitochondria and removes toxic acyls from xenobiotics. Drugs Exp Clin Res 27, 27–49 (2001)

  • [64]G Galli, M Fratelli: Activation of apoptosis by serum deprivation in a teratocarcinoma cell line: inhibition by L-acetylcarnitine. Exp Cell Res 204, 54–60, (1993)

  • [65]RP Revoltella, B Dal Canto, L Caracciolo, CM D’Urso: L-Carnitine and some of its analogs delay the onset of apoptotic cell death initiated in murine C2.8 hepatocytic cells after hepatocyte growth factor deprivation. Biochim Biophys Acta 1224, 333–341 (1994)

  • [66]JW Snyder, ME Kyle, TN Ferraro: L-carnitine delays the killing of cultured hepatocytes by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Arch Biochem Biophys 276, 132–138 (1990)

  • [67]S Moretti, G Famularo, S Marcellini: L-Carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1 infected subjects treated with zidovudine and di-danosine. Antioxid Redox Signal 4, 391–403 (2002)

  • [68]A Virmani, F Gaetani, Z Binienda, A Xu, H Duhart, SF Ali: Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine. Ann N Y Acad Sci 1025, 267–273 (2004)

  • [69]RT Pillich, G Scarsella, G Risuleo: Reduction of apoptosis through the mitochondrial pathway by the administration of acetyl-L-carnitine to mouse fibroblasts in culture. Exp Cell Res 306(1), 1-8 (2005)

  • [70]Z Altun, Y Olgun, P Ercetin, S Aktas, G Kirkim, B Serbetcioglu, N Olgun, EA Guneri: Protective effect of acetyl-l-carnitine against cisplatin ototoxicity: role of apoptosis-related genes and pro-inflammatory cytokines. Cell Prolif 47(1), 72-80

  • [71]N Panahian, M Yoshiura, MD Maines: Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice. J Neurochem 72(3), 1187-1203 (1999)

  • [72]LDi Cesare Mannelli, C Ghelardini, M Calvani, R Nicolai, L Mosconi, E Vivoli, A Pacini, A Bartolini: Protective effect of acetyl-L-carnitine on the apoptotic pathway of peripheral neuropathy. Eur J Neurosci 26, 820–827 (2007)

  • [73]G Traina, R Bernardi, M Rizzo, M Calvani, M Durante, M Brunelli: Acetyl-L-carnitine up-regulates expression of voltage-dependent anion channel in the rat brain. Neurochem Int 48(8), 673-678 (2006)

  • [74]G Traina, R Bernardi, E Cataldo, M Macchi, M Durante, M Brunelli: In the rat brain acetyl-L-carnitine treatment modulates the expression of genes involved in neuronal ceroid lipofuscinosis. Mol Neurobiol 38(2), 146-152 (2008)

  • [75]G Traina, G Federighi, M Brunelli: Up-regulation of kinesin light-chain 1 gene expression by acetyl-L-carnitine: therapeutic possibility in Alzheimer’s disease. Neurochem Int 53(6-8), 244-247 (2008)

  • [76]G Traina, G Federighi, M Macchi, R Bernardi, M Durante, M Brunelli: Modulation of myelin basic protein gene expression by acetyl-L-carnitine. Mol Neurobiol 44(1), 1-6 (2011)

  • [77]D Kasper, R Planells-Cases, J C Fuhrmann, O Scheel, O Zeitz, K Ruether, A Schmitt, M Poët, R Steinfeld, M Schweizer, U Kornak, TJ Jentsch: Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. EMBO J 24, 1079-1091 (2005)

  • [78]JM Holopainen, J Saarikoski, PK Kinnunen, I Järvelä: Elevated lysosomal pH in neuronal ceroid lipofuscinoses (NCLs). Eur J Biochem/FEBS 268, 5851-5856 (2001)

  • [79]M Hayashi, R Miyata, N Tanuma: Oxidative stress in developmental brain disorders. Adv Exp Med Biol 724, 278-90 (2012)

  • [80]H Wei, SJ Kim, Z Zhang, PC Tsai, KE Wisniewski, AB Mukherjee: ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones. Hum Mol Genet 17(4), 469-477 (2008)

  • [81]G Traina, P Bigini, G Federighi, L Sitia, G Paroni, F Fiordaliso, M Salio, C Bendotti, M Brunelli: Lipofuscin accumulation and gene expression in different tissues of mnd mice. Mol Neurobiol 45(2), 247-257 (2012)

  • [82]X Liang, L Wu, T Hand, K Andreasson: Prostaglandin D2 mediates neuronal protection via the DP1 receptor. J Neurochem 92(3), 477-486 (2005)

  • [83]TN Lin, WM Cheung, JS Wu, JJ Chen, H Lin, JJ Chen, JY Liou, SK Shyue, KK Wu: 15d-prostaglandin J2 protects brain from ischemia-reperfusion injury. Arterioscler Thromb Vasc Biol 26(3), 481-487 (2006)

  • [84]A Lal, W Atamna, DW Killilea, JH Suh, BN Ames: Lipoic acid and acetyl-carnitine reverse iron-induced oxidative stress in human fibroblasts. Redox Rep 13(1), 2-10 (2008)

  • [85]M Malaguarnera, L Cammalleri, MP Gargante, M Vacante, V Colonna, M Motta: L-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 86(6), 1738-1744 (2007)

  • [86]M Malaguarnera, G Pistone, G Receputo, R Rapisarda, FB Tomasello, M Motta, D Maugeri: Serum Carnitine Levels in Centenarians. Clin Drug Investig 17, 321-327 (1999)

  • [87]M Malaguarnera: Carnitine derivatives: clinical usefulness. Curr Opin Gastroenterol 28(2), 166-176 (2012)

  • [88]M Frenzel, H Rommelspacher, MD Sugawa, NA Dencher: Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex. Exp Gerontol 45(7-8), 563-572 (2010)

  • [89]G Aliev, J Liu, JC Shenk, K Fischbach, GJ Pacheco, SG Chen, ME Obrenovich, WF Ward, AG Richardson, MA Smith, E Gasimov, G Perry, BN Ames: Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and lipoic acid to aged rats. J Cell Mol Med 13(2), 320-333 (2009)

  • [90]TM Hagen, J Liu, J Lykkesfeldt, CM Wehr, RT Ingersoll, V Vinarsky, JC Bartholomew, BN Ames: Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A 99, 1870-1875 (2002)

  • [91]J Long, F Gao, L Tong, CW Cotman, BN Ames, J Liu: Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. Neurochem Res 34(4), 755-763 (2009)

  • [92]SK Park, K Kim, GP Page, DB Allison, R Weindruch, TA Prolla: Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants. Aging Cell 8(4), 484-495 (2009)

  • [93]MD Seidman, MJ Khan, U Bai, N Shirwany, WS Quirk: Biologic activity of mitochondrial metabolites on aging and age-related hearing loss. Am J Otol 21(2), 161-167 (2000)

  • [94]MF Beal: Bioenergetic approaches for neuroprotection in Parkinson’s disease. Ann Neurol 53 Suppl 3, S39-47, S47-48 (2003)

  • [95]TM Hagen, RT Ingersoll, CM Wehr, J Lykkesfeldt, VVinarsky, JC Bartholomew, MH Song, BN Ames: Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci U S A 95(16), 9562-9566 (1998)

  • [96]TM Hagen, R Moreau, JH Suh, F Visioli: Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-L-carnitine and/or lipoic acid. Ann N Y Acad Sci 959, 491-507 (2002)

  • [97]JH Suh, R Moreau, SH Heath, TM Hagen: Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep 10(1), 52-60 (2005)

  • [98]V Steffen, M Santiago, CP de la Cruz, E Revilla, A Machado, J Cano: Effect of intraventricular injection of 1-methyl-4-phenylpyridinium: protection by acetyl-L-carnitine. Hum Exp Toxicol 14(11), 865-871 (1995)

  • [99]IBodis Wollner, E Chung, MF Ghilardi, A Glover, M Onofrj, P Pasik, Y Samson: Acetyl-levo-carnitine protects against MPTP-induced parkinsonism in primates. J Neural Transm Park Dis Dement Sect 3(1), 63-72 (1991)

  • [100]Z Binienda, A Virmani, B Przybyla-Zawislak, L Schmued: Neuroprotective effect of L-carnitine in the 3-nitropropionic acid (3-NPA)-evoked neurotoxicity in rats. Neurosci Lett 367(2), 264-267 (2004)

  • [101]K Hino, M Nishikawa, E Sato, M Inoue: L-carnitine inhibits hypoglycemia-induced brain damage in the rat. Brain Res 1053, 77-87 (2005)

  • [102]L Palmieri, AM. Persico: Mitochondrial dysfunction in autism spectrum disorders: cause or effect? Biochim Biophys Acta 1797(6-7), 1130-1137 (2010)

  • [103]PA Filipek, J Juranek, MT Nguyen, C Cummings, JJ Gargus: Relative carnitine deficiency in autism. J Autism Dev Disord 34(6), 615-623 (2004)

  • [104]M Calvani, M Lannuccelli, D Colasimone, Z Orfalian. Chronicle of the development of an endogenous substance for dementia: acetyl-lcarnitine. In: Senile Dementias: Early Detection. Ed: A Bes, John Libbey Eurotext (1986)

  • [105]EBonavita: Study of the efficacy and tolerability of L-acetylcarnitine therapy in the senile brain. Int J Clin Pharmacol Ther Toxicol 24(9), 511-516 (1986)

  • [106]A Virmani, Z Binienda: Role of carnitine esters in brain neuropathology. Mol Aspects Med 25(5-6), 533-549 (2004)

  • [107]G.B Stokin, C Lillo, TL Falzone, RG Brusch, E Rockenstein, SL Mount, R Raman, P Davies, E Masliah, DS Williams, LS Goldstein: Axonopathy and transport deficits early in the pathogenesis of Alzheimer’s disease. Science 307 (5713), 1282-1288 (2005)

  • [108]H Takahashi, JM McCaffery, RA Irizarry, JD Boeke: Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription. Mol Cell 23, 207–217 (2006)

  • [109]MG Rosca, H Lemieux, CL Hoppel: Mitochondria in the elderly: is acetylcarnitine a rejuvenator? Adv Drug Deliv Rev 61, 1332–1342 (2009)

  • [110]B Schwer, J Bunkenborg, RO Verdin, JS Andersen, E Verdin: Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci U S A 103, 10224–10229 (2006)

  • [111]DB Lombard, FW Alt, HL Cheng, J Bunkenborg, RS Streeper, R Mostoslavsky, J Kim, G Yancopoulos, D Valenzuela, A Murphy, Y Yang, Y Chen, MD Hirschey, RT Bronson, M Haigis, LP Guarente, RV Farese, Jr, S Weissman, E Verdin, B Schwer: Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 27(24), 8807-8814 (2007)

  • [112]MC Haigis, R Mostoslavsky, KM Haigis, K Fahie, DC Christodoulou, AJ Murphy, DM Valenzuela, GD Yancopoulos, M Karow, G Blander, C Wolberger, TA Prolla, R Weindruch, FW Alt, L. Guarente: SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. Cell 126, 941–954 (2006)

  • [113]BH Ahn, HS Kim, S Song, IH Lee, J Liu, A Vassilopoulos, CX Deng, T Finkel: Arole for the mitochondrial deacetylase SIRT3 in regulat ing energy homeostasis. Proc Natl Acad Sci U S A 105, 14447–14452 (2008)

  • [114]M Morigi, L Perico, C Rota, L Longaretti, S Conti, D Rottoli, R Novelli, G Remuzzi, A Benigni: Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury. J Clin Invest 125(2), 715-726 (2015)

  • [115]S Chiechio, A Caricasole, E Barletta, M Storto, MV Catania, A Copani, M Vertechy, R Nicolai, M Calvani, D Melchiorri, F Nicoletti: L-Acetylcarnitine induces analgesia by selectively up-regulating mGlu2 metabotropic glutamate receptors. Mol Pharmacol 61(5), 989-996 (2002)

  • [116]S Chiechio, A Copani, M Zammataro, G Battaglia, RW 4th Gereau, F Nicoletti: Transcriptional regulation of type-2 metabotropic glutamate receptors: an epigenetic path to novel treatments for chronic pain.Trends Pharmacol Sci 31(4), 153-160 (2010)

  • [117]S Chiechio, FNicoletti: Metabotropic glutamate receptors and the control of chronic pain. Curr Opin Pharmacol 12(1), 28-34 (2012)

  • [118]F Nicoletti, J Bockaert, GL Collingridge, PJ Conn, F Ferraguti, DD Schoepp, JT Wroblewski, JP Pin: Metabotropic glutamate receptors: from the workbench to the bedside. Neuropharmacology 60(7-8), 1017-1041 (2011)

  • [119]PJ Foreman, JR Perez-Polo, L Angelucci, MT Ramacci, G Taglialatela: Effects of acetyl-L-carnitine treatment and stress exposure on the nerve growth factor receptor (p75NGFR) mRNA level in the central nervous system of aged rats. Prog Neuropsychopharmacol Biol Psychiatry 19(1), 117-133 (1995)

  • [120]JH Furlong: Acetyl-l-carnitine: metabolism and applications in clinical practice. Altern Med Rev 1, 85-93 (1996)

  • [121]AA Sima, H Ristic, A Merry, M Kamijo, SA Lattimer, MJ Stevens, DA Greene: Primary preventive and secondary interventionary effects of acetyl-L-carnitine on diabetic neuropathy in the bio-breeding Worcester rat. J Clin Invest 97(8), 1900-1907 (1996)

  • [122]CDe Angelis, C Scarfo, M Falcinelli, E Perna, E Reda, MT Ramacci, L Angelucci: Acetyl-L-carnitine prevents age-dependent structural alterations in rat peripheral nerves and promotes regeneration following sciatic nerve injury in young and senescent rats. Exp Neurol 128(1), 103-114 (1994)

  • [123]P Bigini, S Larini, C Pasquali, V Muzio, T Mennini: Acetyl-L-carnitine shows neuroprotective and neurotrophic activity in primary culture of rat embryo motoneurons. Neurosci Lett 329(3), 334-338 (2002)

  • [124]C Ristori, E Cataldo, ML Zaccardi, G Traina, M Calvani, P Lombardo, R Scuri, M Brunelli: Acetyl-L-carnitine affects nonassociative learning processes in the leech Hirudo medicinalis. Neuroscience 142(4), 931-939 (2006)

  • [125]ML Zaccardi, G Traina, E Cataldo, M Brunelli: Nonassociative learning in the leech Hirudo medicinalis. Behav Brain Res 126(1-2), 81-92 (2001)

  • [126]ML Zaccardi, G Traina, E Cataldo, M Brunelli: Sensitization and dishabituation of swim induction in the leech Hirudo medicinalis: role of serotonin and cyclic AMP. Behav Brain Res 153(2), 317-326 (2004)

  • [127]G Traina, C Ristori, M Brunelli, R Scuri: Acetyl-l-carnitine prevents serotonin-induced behavioural sensitization and dishabituation in Hirudo medicinalis. Behav Brain Res 253, 323-328 (2013)

  • [128]G Traina, R Scuri: Transcription and protein synthesis inhibitors influence long-term effects of acetyl-l-carnitine on non-associative learning in the leech. Neurochem Int 80, 72-78 (2015)

  • [129]G Federighi, M Macchi, R Bernardi, R Scuri, M Brunelli, M Durante, G Traina: Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment. PLoS One 8(1), e53605 (2013)

  • [130]P Lombardo, R Scuri, E Cataldo, M Calvani, R Nicolai, L Mosconi, M Brunelli: Acetyl-L-carnitine induces a sustained potentiation of the afterhyperpolarization. Neuroscience 128(2), 293-303 (2004)

Article Metrics

  • Information

  • Download

  • Contents

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

1 Jun 2016Review

The neurobiology of acetyl-L-carnitine

Giovanna Traina 1,*
Affiliation
Article Info

1 Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Perugia, Via S. Costanzo, 06126 Perugia, Italy

Abstract

A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during beta-oxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies. ALC also has antioxidant and anti-apoptotic activity. Moreover, ALC exhibits positive effects on mitochondrial metabolism, and shows promise in the treatment of aging and neurodegenerative pathologies by slowing the progression of mental deterioration. In addition, ALC plays neuromodulatory effects on both synaptic morphology and synaptic transmission. These effects are likely due to affects of ALC through modulation of gene expression on several targets in the central nervous system.Here, we review the current state of knowledge on effects of ALC in the nervous system.

Keywords

  • Acetyl-L-carnitine
  • Nervous System
  • Gene Expression
  • Neuroprotection
  • Review

References

Cite

Share