Login Register Cart 0
Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Acetyl-L-carnitine and Amyotrophic Lateral Sclerosis: Current Evidence and Potential use

Author(s): Fabiola De Marchi, Sakthipriyan Venkatesan, Massimo Saraceno, Letizia Mazzini and Elena Grossini*

Volume 23, Issue 5, 2024

Published on: 27 April, 2023

Page: [588 - 601] Pages: 14

DOI: 10.2174/1871527322666230330083757

Price: $65

Abstract

Background: The management of neurodegenerative diseases can be frustrating for clinicians, given the limited progress of conventional medicine in this context.

Aim: For this reason, a more comprehensive, integrative approach is urgently needed. Among various emerging focuses for intervention, the modulation of central nervous system energetics, oxidative stress, and inflammation is becoming more and more promising.

Methods: In particular, electrons leakage involved in the mitochondrial energetics can generate reactive oxygen-free radical-related mitochondrial dysfunction that would contribute to the etiopathology of many disorders, such as Alzheimer's and other dementias, Parkinson's disease, multiple sclerosis, stroke, and amyotrophic lateral sclerosis (ALS).

Results: In this context, using agents, like acetyl L-carnitine (ALCAR), provides mitochondrial support, reduces oxidative stress, and improves synaptic transmission.

Conclusion: This narrative review aims to update the existing literature on ALCAR molecular profile, tolerability, and translational clinical potential use in neurodegeneration, focusing on ALS.

Keywords: Amyotrophic lateral sclerosis, motor neuron diseases, TDP-43, central nervous system, ALCAR, MNDs.

« Previous Next »
Graphical Abstract

[1]
Longinetti E, Fang F. Epidemiology of amyotrophic lateral sclerosis: An update of recent literature. Curr Opin Neurol 2019; 32(5): 771-6.
[http://dx.doi.org/10.1097/WCO.0000000000000730] [PMID: 31361627]
[2]
Chiò A, Calvo A, Moglia C, Mazzini L, Mora G. Phenotypic heterogeneity of amyotrophic lateral sclerosis: A population based study. J Neurol Neurosurg Psychiatry 2011; 82(7): 740-6.
[http://dx.doi.org/10.1136/jnnp.2010.235952] [PMID: 21402743]
[3]
Feldman EL, Goutman SA, Petri S, et al. Amyotrophic lateral sclerosis. Lancet 2022; 400(10360): 1363-80.
[http://dx.doi.org/10.1016/S0140-6736(22)01272-7] [PMID: 36116464]
[4]
De Marchi F, Carrarini C, De Martino A, et al. Cognitive dysfunction in amyotrophic lateral sclerosis: Can we predict it? Neurol Sci 2021; 42(6): 2211-22.
[http://dx.doi.org/10.1007/s10072-021-05188-0] [PMID: 33772353]
[5]
Huynh W, Ahmed R, Mahoney CJ, et al. The impact of cognitive and behavioral impairment in amyotrophic lateral sclerosis. Expert Rev Neurother 2020; 20(3): 281-93.
[http://dx.doi.org/10.1080/14737175.2020.1727740] [PMID: 32031423]
[6]
Bersano E, Sarnelli MF, Solara V, Iazzolino B, Peotta L, De Marchi F, et al. Decline of cognitive and behavioral functions in amyotrophic lateral sclerosis: A longitudinal study. Amyotroph Lateral Scler Frontotemporal Degener 2020; 21(5-6): 373.
[http://dx.doi.org/10.1080/21678421.2020.1771732] [PMID: 32484726]
[7]
Barber SC, Shaw PJ. Oxidative stress in ALS: Key role in motor neuron injury and therapeutic target. Free Radic Biol Med 2010; 48(5): 629-41.
[http://dx.doi.org/10.1016/j.freeradbiomed.2009.11.018] [PMID: 19969067]
[8]
McAlary L, Plotkin SS, Yerbury JJ, Cashman NR. Prion-like propagation of protein misfolding and aggregation in amyotrophic lateral sclerosis. Front Mol Neurosci 2019; 12: 262.
[http://dx.doi.org/10.3389/fnmol.2019.00262] [PMID: 31736708]
[9]
Shaw PJ, Ince PG. Glutamate, excitotoxicity and amyotrophic lateral sclerosis. J Neurol 1997; 244(S2): S3-S14.
[http://dx.doi.org/10.1007/BF03160574] [PMID: 9178165]
[10]
Schreiber S, Schreiber F, Garz C, et al. Toward in vivo determination of peripheral nervous system immune activity in amyotrophic lateral sclerosis. Muscle Nerve 2019; 59(5): 567-76.
[http://dx.doi.org/10.1002/mus.26444] [PMID: 30734322]
[11]
Liu Z, Cheng X, Zhong S, et al. Peripheral and central nervous system immune response crosstalk in amyotrophic lateral sclerosis. Front Neurosci 2020; 14: 575.
[http://dx.doi.org/10.3389/fnins.2020.00575] [PMID: 32612503]
[12]
Miller RG, Mitchell JD, Moore DH. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev 2012; 2012(3): CD001447.
[http://dx.doi.org/10.1002/14651858.CD001447] [PMID: 12076411]
[13]
Chiò A, Mazzini L, Mora G. Disease-modifying therapies in amyotrophic lateral sclerosis. Neuropharmacology 2020; 167: 107986.
[http://dx.doi.org/10.1016/j.neuropharm.2020.107986] [PMID: 32062193]
[14]
Johnson SA, Fang T, De Marchi F, et al. Pharmacotherapy for amyotrophic lateral sclerosis: A review of approved and upcoming agents. Drugs 2022; 82(13): 1367-88.
[http://dx.doi.org/10.1007/s40265-022-01769-1] [PMID: 36121612]
[15]
Bedlack RS, Joyce N, Carter GT, Paganoni S, Karam C. Complementary and alternative therapies in amyotrophic lateral sclerosis. Neurol Clin 2015; 33(4): 909-36.
[http://dx.doi.org/10.1016/j.ncl.2015.07.008] [PMID: 26515629]
[16]
Boylan K. Familial amyotrophic lateral sclerosis. Neurol Clin 2015; 33(4): 807-30.
[http://dx.doi.org/10.1016/j.ncl.2015.07.001] [PMID: 26515623]
[17]
Paré B, Lehmann M, Beaudin M, et al. Misfolded SOD1 pathology in sporadic amyotrophic lateral sclerosis. Sci Rep 2018; 8(1): 14223.
[http://dx.doi.org/10.1038/s41598-018-31773-z] [PMID: 30242181]
[18]
Pansarasa O, Bordoni M, Diamanti L, Sproviero D, Gagliardi S, Cereda C. SOD1 in amyotrophic lateral sclerosis:“Ambivalent” behavior connected to the disease. Int J Mol Sci 2018; 19(5): 1345.
[http://dx.doi.org/10.3390/ijms19051345] [PMID: 29751510]
[19]
Radunovíc A, Leigh PN. Cu/Zn superoxide dismutase gene mutations in amyotrophic lateral sclerosis: correlation between genotype and clinical features. J Neurol Neurosurg Psychiatry 1996; 61(6): 565-72.
[http://dx.doi.org/10.1136/jnnp.61.6.565] [PMID: 8971099]
[20]
Le Gall L, Anakor E, Connolly O, Vijayakumar U, Duddy W, Duguez S. Molecular and cellular mechanisms affected in ALS. J Pers Med 2020; 10(3): 101.
[http://dx.doi.org/10.3390/jpm10030101] [PMID: 32854276]
[21]
Shibata N, Asayama K, Hirano A, Kobayashi M. Immunohistochemical study on superoxide dismutases in spinal cords from autopsied patients with amyotrophic lateral sclerosis. Dev Neurosci 1996; 18(5-6): 492-8.
[http://dx.doi.org/10.1159/000111445] [PMID: 8940623]
[22]
Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993; 362(6415): 59-62.
[http://dx.doi.org/10.1038/362059a0] [PMID: 8446170]
[23]
Valentine JS, Hart PJ. Misfolded CuZnSOD and amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 2003; 100(7): 3617-22.
[http://dx.doi.org/10.1073/pnas.0730423100] [PMID: 12655070]
[24]
McAlary L, Aquilina JA, Yerbury JJ. Susceptibility of mutant SOD1 to form a destabilized monomer predicts cellular aggregation and toxicity but not in vitro aggregation propensity. Front Neurosci 2016; 10: 499.
[http://dx.doi.org/10.3389/fnins.2016.00499] [PMID: 27867347]
[25]
Nishitoh H, Kadowaki H, Nagai A, et al. ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev 2008; 22(11): 1451-64.
[http://dx.doi.org/10.1101/gad.1640108] [PMID: 18519638]
[26]
Dangoumau A, Marouillat S, Burlaud Gaillard J, et al. Inhibition of pathogenic mutant SOD1 aggregation in cultured motor neuronal cells by prevention of its SUMOylation on lysine 75. Neurodegener Dis 2016; 16(3-4): 161-71.
[http://dx.doi.org/10.1159/000439254] [PMID: 26605782]
[27]
Sone J, Niwa J, Kawai K, et al. Dorfin ameliorates phenotypes in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci Res 2010; 88(1): 123-35.
[http://dx.doi.org/10.1002/jnr.22175] [PMID: 19610091]
[28]
Yung C, Sha D, Li L, Chin LS. Parkin protects against misfolded SOD1 toxicity by promoting its aggresome formation and autophagic clearance. Mol Neurobiol 2016; 53(9): 6270-87.
[http://dx.doi.org/10.1007/s12035-015-9537-z] [PMID: 26563499]
[29]
Maurel C, Dangoumau A, Marouillat S, et al. Causative genes in amyotrophic lateral sclerosis and protein degradation pathways: a link to neurodegeneration. Mol Neurobiol 2018; 55(8): 6480-99.
[http://dx.doi.org/10.1007/s12035-017-0856-0] [PMID: 29322304]
[30]
Ferraiuolo L, Higginbottom A, Heath PR, et al. Dysregulation of astrocyte-motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain 2011; 134(9): 2627-41.
[http://dx.doi.org/10.1093/brain/awr193] [PMID: 21908873]
[31]
Keating SS, San Gil R, Swanson MEV, Scotter EL, Walker AK. TDP-43 pathology: From noxious assembly to therapeutic removal. Prog Neurobiol 2022; 211: 102229.
[http://dx.doi.org/10.1016/j.pneurobio.2022.102229] [PMID: 35101542]
[32]
Kim G, Gautier O, Tassoni-Tsuchida E, Ma XR, Gitler AD. ALS genetics: Gains, losses, and implications for future therapies. Neuron 2020; 108(5): 822-42.
[http://dx.doi.org/10.1016/j.neuron.2020.08.022] [PMID: 32931756]
[33]
McCann EP, Williams KL, Fifita JA, et al. The genotype-phenotype landscape of familial amyotrophic lateral sclerosis in Australia. Clin Genet 2017; 92(3): 259-66.
[http://dx.doi.org/10.1111/cge.12973] [PMID: 28105640]
[34]
Kabashi E, Valdmanis PN, Dion P, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 2008; 40(5): 572-4.
[http://dx.doi.org/10.1038/ng.132] [PMID: 18372902]
[35]
Pesiridis GS, Lee VMY, Trojanowski JQ. Mutations in TDP-43 link glycine-rich domain functions to amyotrophic lateral sclerosis. Hum Mol Genet 2009; 18(R2): R156-62.
[http://dx.doi.org/10.1093/hmg/ddp303] [PMID: 19808791]
[36]
Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 2008; 319(5870): 1668-72.
[http://dx.doi.org/10.1126/science.1154584] [PMID: 18309045]
[37]
Alami NH, Smith RB, Carrasco MA, et al. Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations. Neuron 2014; 81(3): 536-43.
[http://dx.doi.org/10.1016/j.neuron.2013.12.018] [PMID: 24507191]
[38]
Budini M, Romano V, Quadri Z, Buratti E, Baralle FE. TDP-43 loss of cellular function through aggregation requires additional structural determinants beyond its C-terminal Q/N prion-like domain. Hum Mol Genet 2015; 24(1): 9-20.
[http://dx.doi.org/10.1093/hmg/ddu415] [PMID: 25122661]
[39]
Boland B, Yu WH, Corti O, et al. Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing. Nat Rev Drug Discov 2018; 17(9): 660-88.
[http://dx.doi.org/10.1038/nrd.2018.109] [PMID: 30116051]
[40]
Klaips CL, Jayaraj GG, Hartl FU. Pathways of cellular proteostasis in aging and disease. J Cell Biol 2018; 217(1): 51-63.
[http://dx.doi.org/10.1083/jcb.201709072] [PMID: 29127110]
[41]
Deng HX, Chen W, Hong ST, et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 2011; 477(7363): 211-5.
[http://dx.doi.org/10.1038/nature10353] [PMID: 21857683]
[42]
Teyssou E, Takeda T, Lebon V, et al. Mutations in SQSTM1 encoding p62 in amyotrophic lateral sclerosis: genetics and neuropathology. Acta Neuropathol 2013; 125(4): 511-22.
[http://dx.doi.org/10.1007/s00401-013-1090-0] [PMID: 23417734]
[43]
van der Zee J, Gijselinck I, Van Mossevelde S, et al. TBK1 mutation spectrum in an extended european patient cohort with frontotemporal dementia and amyotrophic lateral sclerosis. Hum Mutat 2017; 38(3): 297-309.
[http://dx.doi.org/10.1002/humu.23161] [PMID: 28008748]
[44]
Huang B, Wu Q, Zhou H, Huang C, Xia XG. Increased Ubqln2 expression causes neuron death in transgenic rats. J Neurochem 2016; 139(2): 285-93.
[http://dx.doi.org/10.1111/jnc.13748] [PMID: 27456931]
[45]
Wu Q, Liu M, Huang C, et al. Pathogenic Ubqln2 gains toxic properties to induce neuron death. Acta Neuropathol 2015; 129(3): 417-28.
[http://dx.doi.org/10.1007/s00401-014-1367-y] [PMID: 25388785]
[46]
Hjerpe R, Bett JS, Keuss MJ, et al. UBQLN2 mediates autophagy-independent protein aggregate clearance by the proteasome. Cell 2016; 166(4): 935-49.
[http://dx.doi.org/10.1016/j.cell.2016.07.001] [PMID: 27477512]
[47]
Osaka M, Ito D, Suzuki N. Disturbance of proteasomal and autophagic protein degradation pathways by amyotrophic lateral sclerosis-linked mutations in ubiquilin 2. Biochem Biophys Res Commun 2016; 472(2): 324-31.
[http://dx.doi.org/10.1016/j.bbrc.2016.02.107] [PMID: 26944018]
[48]
Wu JJ, Cai A, Greenslade JE, et al. ALS/FTD mutations in UBQLN2 impede autophagy by reducing autophagosome acidification through loss of function. Proc Natl Acad Sci USA 2020; 117(26): 15230-41.
[http://dx.doi.org/10.1073/pnas.1917371117] [PMID: 32513711]
[49]
Ayaki T, Ito H, Fukushima H, et al. Immunoreactivity of valosin-containing protein in sporadic amyotrophic lateral sclerosis and in a case of its novel mutant. Acta Neuropathol Commun 2014; 2(1): 172.
[http://dx.doi.org/10.1186/s40478-014-0172-0] [PMID: 25492614]
[50]
Harley J, Hagemann C, Serio A, Patani R. TDP-43 and FUS mislocalization in VCP mutant motor neurons is reversed by pharmacological inhibition of the VCP D2 ATPase domain. Brain Commun 2021; 3(3): fcab166.
[http://dx.doi.org/10.1093/braincomms/fcab166] [PMID: 34396115]
[51]
Ju JS, Fuentealba RA, Miller SE, et al. Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease. J Cell Biol 2009; 187(6): 875-88.
[http://dx.doi.org/10.1083/jcb.200908115] [PMID: 20008565]
[52]
Kurashige T, Kuramochi M, Ohsawa R, et al. Optineurin defects cause TDP43-pathology with autophagic vacuolar formation. Neurobiol Dis 2021; 148: 105215.
[http://dx.doi.org/10.1016/j.nbd.2020.105215] [PMID: 33296728]
[53]
Shen WC, Li HY, Chen GC, Chern Y, Tu P. Mutations in the ubiquitin-binding domain of OPTN/optineurin interfere with autophagy-mediated degradation of misfolded proteins by a dominant-negative mechanism. Autophagy 2015; 11(4): 685-700.
[http://dx.doi.org/10.4161/auto.36098] [PMID: 25484089]
[54]
Chen HJ, Mitchell JC, Novoselov S, et al. The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis. Brain 2016; 139(5): 1417-32.
[http://dx.doi.org/10.1093/brain/aww028] [PMID: 26936937]
[55]
Gorter RP, Stephenson J, Nutma E, et al. Rapidly progressive amyotrophic lateral sclerosis is associated with microglial reactivity and small heat shock protein expression in reactive astrocytes. Neuropathol Appl Neurobiol 2019; 45(5): 459-75.
[http://dx.doi.org/10.1111/nan.12525] [PMID: 30346063]
[56]
Wang P, Wander CM, Yuan CX, Bereman MS, Cohen TJ. Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program. Nat Commun 2017; 8(1): 82.
[http://dx.doi.org/10.1038/s41467-017-00088-4] [PMID: 28724966]
[57]
Farhan SMK, Howrigan DP, Abbott LE, et al. Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein. Nat Neurosci 2019; 22(12): 1966-74.
[http://dx.doi.org/10.1038/s41593-019-0530-0] [PMID: 31768050]
[58]
Lin LT-W, Razzaq A, Di Gregorio SE, Hong S, Charles B, Lopes MH, et al. Hsp90 and its co- chaperone Sti1 control TDP-43 misfolding and toxicity. FASEB J 2021; 35(5): e21594.
[http://dx.doi.org/10.1096/fj.202002645R]
[59]
Zhang YJ, Gendron TF, Xu YF, Ko LW, Yen SH, Petrucelli L. Phosphorylation regulates proteasomal-mediated degradation and solubility of TAR DNA binding protein-43 C-terminal fragments. Mol Neurodegener 2010; 5(1): 33.
[http://dx.doi.org/10.1186/1750-1326-5-33] [PMID: 20804554]
[60]
Coyne AN, Lorenzini I, Chou CC, et al. Post-transcriptional inhibition of Hsc70-4/HSPA8 expression leads to synaptic vesicle cycling defects in multiple models of ALS. Cell Rep 2017; 21(1): 110-25.
[http://dx.doi.org/10.1016/j.celrep.2017.09.028] [PMID: 28978466]
[61]
Carlomagno Y, Zhang Y, Davis M, et al. Casein kinase II induced polymerization of soluble TDP-43 into filaments is inhibited by heat shock proteins. PLoS One 2014; 9(3): e90452.
[http://dx.doi.org/10.1371/journal.pone.0090452] [PMID: 24595055]
[62]
Huang CC, Bose JK, Majumder P, et al. Metabolism and mismetabolism of the neuropathological signature protein TDP-43. J Cell Sci 2014; 127(Pt 14): jcs.136150.
[http://dx.doi.org/10.1242/jcs.136150] [PMID: 24860144]
[63]
Shaw PJ, Forrest V, Ince PG, Richardson JP, Wastell HJ. CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 1995; 4(2): 209-16.
[http://dx.doi.org/10.1006/neur.1995.0026] [PMID: 7583686]
[64]
Rothstein JD, Tsai G, Kuncl RW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 1990; 28(1): 18-25.
[http://dx.doi.org/10.1002/ana.410280106] [PMID: 2375630]
[65]
Sasaki S, Komori T, Iwata M. Excitatory amino acid transporter 1 and 2 immunoreactivity in the spinal cord in amyotrophic lateral sclerosis. Acta Neuropathol 2000; 100(2): 138-44.
[http://dx.doi.org/10.1007/s004019900159] [PMID: 10963360]
[66]
Bristol LA, Rothstein JD. Glutamate transporter gene expression in amyotrophic lateral sclerosis motor cortex. Ann Neurol 1996; 39(5): 676-9.
[http://dx.doi.org/10.1002/ana.410390519] [PMID: 8619555]
[67]
Wang Y, Qin Z. Molecular and cellular mechanisms of excitotoxic neuronal death. Apoptosis 2010; 15(11): 1382-402.
[http://dx.doi.org/10.1007/s10495-010-0481-0] [PMID: 20213199]
[68]
Virgo L, de Belleroche J. Induction of the immediate early gene c-jun in human spinal cord in amyotrophic lateral sclerosis with concomitant loss of NMDA receptor NR-1 and glycine transporter mRNA. Brain Res 1995; 676(1): 196-204.
[http://dx.doi.org/10.1016/0006-8993(95)00052-R] [PMID: 7796170]
[69]
Wagey R, Pelech SL, Duronio V, Krieger C. Phosphatidylinositol 3-kinase: increased activity and protein level in amyotrophic lateral sclerosis. J Neurochem 1998; 71(2): 716-22.
[http://dx.doi.org/10.1046/j.1471-4159.1998.71020716.x] [PMID: 9681462]
[70]
De Belleroche JS, Kondori NR, Paul P, Robbins J, Liu K, Hildyard J, et al. Focus on the role of D-serine and D-amino acid oxidase in amyotrophic lateral sclerosis/motor neuron disease (ALS). Front Mol Biosci 2018; 5: 8.
[http://dx.doi.org/10.3389/fmolb.2018.00008]
[71]
Gille B, De Schaepdryver M, Dedeene L, et al. Inflammatory markers in cerebrospinal fluid: independent prognostic biomarkers in amyotrophic lateral sclerosis? J Neurol Neurosurg Psychiatry 2019; 90(12): jnnp-2018-319586.
[http://dx.doi.org/10.1136/jnnp-2018-319586] [PMID: 31175169]
[72]
Paul P, de Belleroche J. The role of D-serine and glycine as co-agonists of NMDA receptors in motor neuron degeneration and amyotrophic lateral sclerosis (ALS). Front Synaptic Neurosci 2014; 6: 10.
[http://dx.doi.org/10.3389/fnsyn.2014.00010] [PMID: 24795623]
[73]
Corona JC, Tapia R. AMPA receptor activation, but not the accumulation of endogenous extracellular glutamate, induces paralysis and motor neuron death in rat spinal cord in vivo. J Neurochem 2004; 89(4): 988-97.
[http://dx.doi.org/10.1111/j.1471-4159.2004.02383.x] [PMID: 15140197]
[74]
Kawahara Y, Kwak S, Sun H, et al. Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS. J Neurochem 2003; 85(3): 680-9.
[http://dx.doi.org/10.1046/j.1471-4159.2003.01703.x] [PMID: 12694394]
[75]
Konen LM, Wright AL, Royle GA, et al. A new mouse line with reduced GluA2 Q/R site RNA editing exhibits loss of dendritic spines, hippocampal CA1-neuron loss, learning and memory impairments and NMDA receptor-independent seizure vulnerability. Mol Brain 2020; 13(1): 27.
[http://dx.doi.org/10.1186/s13041-020-0545-1] [PMID: 32102661]
[76]
Bogaert E, Van Damme P, Poesen K, et al. VEGF protects motor neurons against excitotoxicity by upregulation of GluR2. Neurobiol Aging 2010; 31(12): 2185-91.
[http://dx.doi.org/10.1016/j.neurobiolaging.2008.12.007] [PMID: 19185395]
[77]
Takuma H, Kwak S, Yoshizawa T, Kanazawa I. Reduction of GluR2 RNA editing, a molecular change that increases calcium influx through AMPA receptors, selective in the spinal ventral gray of patients with amyotrophic lateral sclerosis. Ann Neurol 1999; 46(6): 806-15.
[http://dx.doi.org/10.1002/1531-8249(199912)46:6<806:AID-ANA2>3.0.CO;2-S] [PMID: 10589532]
[78]
Heath PR, Tomkins J, Ince PG, Shaw PJ. Quantitative assessment of AMPA receptor mRNA in human spinal motor neurons isolated by laser capture microdissection. Neuroreport 2002; 13(14): 1753-7.
[http://dx.doi.org/10.1097/00001756-200210070-00012] [PMID: 12395117]
[79]
Milanese M, Zappettini S, Onofri F, et al. Abnormal exocytotic release of glutamate in a mouse model of amyotrophic lateral sclerosis. J Neurochem 2011; 116(6): 1028-42.
[http://dx.doi.org/10.1111/j.1471-4159.2010.07155.x] [PMID: 21175617]
[80]
van Zundert B, Peuscher MH, Hynynen M, et al. Neonatal neuronal circuitry shows hyperexcitable disturbance in a mouse model of the adult-onset neurodegenerative disease amyotrophic lateral sclerosis. J Neurosci 2008; 28(43): 10864-74.
[http://dx.doi.org/10.1523/JNEUROSCI.1340-08.2008] [PMID: 18945894]
[81]
Higuchi M, Maas S, Single FN, et al. Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature 2000; 406(6791): 78-81.
[http://dx.doi.org/10.1038/35017558] [PMID: 10894545]
[82]
Aizawa H, Sawada J, Hideyama T, et al. TDP-43 pathology in sporadic ALS occurs in motor neurons lacking the RNA editing enzyme ADAR2. Acta Neuropathol 2010; 120(1): 75-84.
[http://dx.doi.org/10.1007/s00401-010-0678-x] [PMID: 20372915]
[83]
Shaw PJ, Williams TL, Slade JY, Eggett CJ, Ince PG. Low expression of GluR2 AMPA receptor subunit protein by human motor neurons. Neuroreport 1999; 10(2): 261-5.
[http://dx.doi.org/10.1097/00001756-199902050-00011] [PMID: 10203319]
[84]
Vandenberghe W, Robberecht W, Brorson JR. AMPA receptor calcium permeability, GluR2 expression, and selective motoneuron vulnerability. J Neurosci 2000; 20(1): 123-32.
[http://dx.doi.org/10.1523/JNEUROSCI.20-01-00123.2000] [PMID: 10627588]
[85]
Hideyama T, Yamashita T, Suzuki T, et al. Induced loss of ADAR2 engenders slow death of motor neurons from Q/R site-unedited GluR2. J Neurosci 2010; 30(36): 11917-25.
[http://dx.doi.org/10.1523/JNEUROSCI.2021-10.2010] [PMID: 20826656]
[86]
King AE, Woodhouse A, Kirkcaldie MTK, Vickers JC. Excitotoxicity in ALS: Overstimulation, or overreaction? Exp Neurol 2016; 275(Pt 1): 162-71.
[http://dx.doi.org/10.1016/j.expneurol.2015.09.019] [PMID: 26584004]
[87]
Shi Y, Hung ST, Rocha G, et al. Identification and therapeutic rescue of autophagosome and glutamate receptor defects in C9ORF72 and sporadic ALS neurons. JCI Insight 2019; 4(15): e127736.
[http://dx.doi.org/10.1172/jci.insight.127736] [PMID: 31310593]
[88]
Tang D, Sheng J, Xu L, et al. Cryo-EM structure of C9ORF72-SMCR8-WDR41 reveals the role as a GAP for Rab8a and Rab11a. Proc Natl Acad Sci USA 2020; 117(18): 9876-83.
[http://dx.doi.org/10.1073/pnas.2002110117] [PMID: 32303654]
[89]
Di Cesare Mannelli L, Tomassoni D, Bramanti V, Ghelardini C, Amenta F, Pacini A. Treatment with acetyl-L-carnitine exerts a neuroprotective effect in the sciatic nerve following loose ligation: a functional and microanatomical study. Neural Regen Res 2018; 13(4): 692-8.
[http://dx.doi.org/10.4103/1673-5374.230297] [PMID: 29722322]
[90]
Kwon OS, Chung YB. Hplc determination and pharmacokinetics of endogenous acetyl-l-carnitine (alc) in human volunteers orally administered a single dose of alc. Arch Pharm Res 2004; 27(6): 676-81.
[http://dx.doi.org/10.1007/BF02980169] [PMID: 15283472]
[91]
Piovesan P, Pacifici L, Taglialatela G, Ramacci MT, Angelucci L. Acetyl-l-carnitine treatment increases choline acetyltransferase activity and NGF levels in the CNS of adult rats following total fimbria-fornix transection. Brain Res 1994; 633(1-2): 77-82.
[http://dx.doi.org/10.1016/0006-8993(94)91524-5] [PMID: 8137174]
[92]
Holder BR, McNaney CA, Luchetti D, Schaeffer E, Drexler DM. Bioanalysis of acetylcarnitine in cerebrospinal fluid by HILIC-mass spectrometry. Biomed Chromatogr 2015; 29(9): 1375-9.
[http://dx.doi.org/10.1002/bmc.3433] [PMID: 25712252]
[93]
Bene J, Hadzsiev K, Melegh B. Role of carnitine and its derivatives in the development and management of type 2 diabetes. Nutr Diabetes 2018; 8(1): 8.
[http://dx.doi.org/10.1038/s41387-018-0017-1] [PMID: 29549241]
[94]
Indiveri C, Iacobazzi V, Tonazzi A, et al. The mitochondrial carnitine/acylcarnitine carrier: Function, structure and physiopathology. Mol Aspects Med 2011; 32(4-6): 223-33.
[http://dx.doi.org/10.1016/j.mam.2011.10.008] [PMID: 22020112]
[95]
Evans AM, Fornasini G. Pharmacokinetics of L-Carnitine. Clin Pharmacokinet 2003; 42(11): 941-67.
[http://dx.doi.org/10.2165/00003088-200342110-00002] [PMID: 12908852]
[96]
Ferreira GC, McKenna MC. L-Carnitine and acetyl-L-carnitine roles and neuroprotection in developing brain. Neurochem Res 2017; 42(6): 1661-75.
[http://dx.doi.org/10.1007/s11064-017-2288-7] [PMID: 28508995]
[97]
Jones LL, McDonald DA, Borum PR. Acylcarnitines: Role in brain. Prog Lipid Res 2010; 49(1): 61-75.
[http://dx.doi.org/10.1016/j.plipres.2009.08.004] [PMID: 19720082]
[98]
Evangeliou A, Vlassopoulos D. Carnitine metabolism and deficit--when supplementation is necessary? Curr Pharm Biotechnol 2003; 4(3): 211-9.
[http://dx.doi.org/10.2174/1389201033489829] [PMID: 12769764]
[99]
Duran M, Loof NE, Ketting D, Dorland L. Secondary carnitine deficiency. J Clin Chem Clin Biochem 1990; 28(5): 359-63.
[PMID: 2199597]
[100]
Komlósi K, Havasi V, Bene J, et al. Histopathologic abnormalities of the lymphoreticular tissues in organic cation transporter 2 deficiency: evidence for impaired B cell maturation. J Pediatr 2007; 150(1): 109-111.e2.
[http://dx.doi.org/10.1016/j.jpeds.2006.09.042] [PMID: 17188629]
[101]
Duranay M, Akay H, Yilmaz FM. Şeneş M, Tekeli N, Yücel D. Effects of L-carnitine infusions on inflammatory and nutritional markers in haemodialysis patients. Nephrol Dial Transplant 2006; 21(11): 3211-4.
[http://dx.doi.org/10.1093/ndt/gfl356] [PMID: 16861734]
[102]
Calò LA, Pagnin E, Davis PA, et al. Antioxidant effect of l-carnitine and its short chain esters. Int J Cardiol 2006; 107(1): 54-60.
[http://dx.doi.org/10.1016/j.ijcard.2005.02.053] [PMID: 16337498]
[103]
Schreiber B. Levocarnitine and dialysis: a review. Nutr Clin Pract 2005; 20(2): 218-43.
[http://dx.doi.org/10.1177/0115426505020002218] [PMID: 16207659]
[104]
Virmani MA, Caso V, Spadoni A, Rossi S, Russo F, Gaetani F. 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 2001; 939(1): 162-78.
[http://dx.doi.org/10.1111/j.1749-6632.2001.tb03623.x] [PMID: 11462768]
[105]
Scafidi S, Racz J, Hazelton J, McKenna MC, Fiskum G. Neuroprotection by acetyl-L-carnitine after traumatic injury to the immature rat brain. Dev Neurosci 2010; 32(5-6): 480-7.
[http://dx.doi.org/10.1159/000323178] [PMID: 21228558]
[106]
Wilson ADH, Hart A, Brännström T, Wiberg M, Terenghi G. Delayed acetyl-l-carnitine administration and its effect on sensory neuronal rescue after peripheral nerve injury. J Plast Reconstr Aesthet Surg 2007; 60(2): 114-8.
[http://dx.doi.org/10.1016/j.bjps.2006.04.017] [PMID: 17223507]
[107]
Calabrese V, Ravagna A, Colombrita C, et al. Acetylcarnitine induces heme oxygenase in rat astrocytes and protects against oxidative stress: Involvement of the transcription factor Nrf2. J Neurosci Res 2005; 79(4): 509-21.
[http://dx.doi.org/10.1002/jnr.20386] [PMID: 15641110]
[108]
Xu S, Waddell J, Zhu W, et al. In vivo longitudinal proton magnetic resonance spectroscopy on neonatal hypoxic-ischemic rat brain injury: Neuroprotective effects of acetyl-L-carnitine. Magn Reson Med 2015; 74(6): 1530-42.
[http://dx.doi.org/10.1002/mrm.25537] [PMID: 25461739]
[109]
Scafidi S, Fiskum G, Lindauer SL, et al. Metabolism of acetyl-l-carnitine for energy and neurotransmitter synthesis in the immature rat brain. J Neurochem 2010; 114(3): 820-31.
[http://dx.doi.org/10.1111/j.1471-4159.2010.06807.x] [PMID: 20477950]
[110]
Aureli T, Miccheli A, Di Cocco ME, et al. Effect of acetyl-L-carnitine on recovery of brain phosphorus metabolites and lactic acid level during reperfusion after cerebral ischemia in the rat study by 13P-and 1H-NMR spectroscopy. Brain Res 1994; 643(1-2): 92-9.
[http://dx.doi.org/10.1016/0006-8993(94)90013-2] [PMID: 8032936]
[111]
White HL, Scates PW. Acetyl-l-carnitine as a precursor of acetylcholine. Neurochem Res 1990; 15(6): 597-601.
[http://dx.doi.org/10.1007/BF00973749] [PMID: 2215852]
[112]
Zanelli SA, Solenski NJ, Rosenthal RE, Fiskum G. Mechanisms of ischemic neuroprotection by acetyl-L-carnitine. Ann N Y Acad Sci 2005; 1053(1): 153-61.
[http://dx.doi.org/10.1196/annals.1344.013] [PMID: 16179519]
[113]
Janiri L, Falcone M, Persico A, Tempesta E. Activity of L-carnitine and L-acetylcarnitine on cholinoceptive neocortical neurons of the rat in vivo. J Neural Transm (Vienna) 1991; 86(2): 135-46.
[http://dx.doi.org/10.1007/BF01250574] [PMID: 1683239]
[114]
Chan DC. Mitochondrial dynamics in disease. N Engl J Med 2007; 356(17): 1707-9.
[http://dx.doi.org/10.1056/NEJMp078040] [PMID: 17460225]
[115]
Marcovina SM, Sirtori C, Peracino A, et al. Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine. Transl Res 2013; 161(2): 73-84.
[http://dx.doi.org/10.1016/j.trsl.2012.10.006] [PMID: 23138103]
[116]
Neubauer S. The failing heart--an engine out of fuel. N Engl J Med 2007; 356(11): 1140-51.
[http://dx.doi.org/10.1056/NEJMra063052] [PMID: 17360992]
[117]
Lenaz G. Mitochondria and reactive oxygen species. Which role in physiology and pathology? Adv mitochondrial Med 2012; 942: 93-136.
[http://dx.doi.org/10.1007/978-94-007-2869-1_5] [PMID: 22399420]
[118]
Wong HS, Dighe PA, Mezera V, Monternier PA, Brand MD. Production of superoxide and hydrogen peroxide from specific mitochondrial sites under different bioenergetic conditions. J Biol Chem 2017; 292(41): 16804-9.
[http://dx.doi.org/10.1074/jbc.R117.789271] [PMID: 28842493]
[119]
Grossini E, Farruggio S, Raina G, Mary D, Deiro G, Gentilli S. Effects of genistein on differentiation and viability of human visceral adipocytes. Nutrients 2018; 10(8): 978.
[http://dx.doi.org/10.3390/nu10080978] [PMID: 30060502]
[120]
Di Meo S, Reed TT, Venditti P, Victor VM. Role of ROS and RNS sources in physiological and pathological conditions. Oxid Med Cell Longev 2016; 2016: 1-44.
[http://dx.doi.org/10.1155/2016/1245049] [PMID: 27478531]
[121]
Green MJ, Hill HAO. Chemistry of dioxygen. Methods Enzymol 1984; 105: 3-22.
[http://dx.doi.org/10.1016/S0076-6879(84)05004-7] [PMID: 6328186]
[122]
Hulsmans M, Van Dooren E, Holvoet P. Mitochondrial reactive oxygen species and risk of atherosclerosis. Curr Atheroscler Rep 2012; 14(3): 264-76.
[http://dx.doi.org/10.1007/s11883-012-0237-0] [PMID: 22350585]
[123]
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809): 239-47.
[http://dx.doi.org/10.1038/35041687] [PMID: 11089981]
[124]
Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med 2016; 95: 27-42.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.02.028] [PMID: 26923386]
[125]
Rhee SG, Kil IS. Multiple functions and regulation of mammalian peroxiredoxins. Annu Rev Biochem 2017; 86(1): 749-75.
[http://dx.doi.org/10.1146/annurev-biochem-060815-014431] [PMID: 28226215]
[126]
Schmidt HHHW, Stocker R, Vollbracht C, et al. Antioxidants in translational medicine. Antioxid Redox Signal 2015; 23(14): 1130-43.
[http://dx.doi.org/10.1089/ars.2015.6393] [PMID: 26154592]
[127]
Sies H. Oxidative stress: Concept and some practical aspects. Antioxidants 2020; 9(9): 852.
[http://dx.doi.org/10.3390/antiox9090852] [PMID: 32927924]
[128]
Sies H, Berndt C, Jones DP. Oxidative Stress. Annu Rev Biochem 2017; 86(1): 715-48.
[http://dx.doi.org/10.1146/annurev-biochem-061516-045037] [PMID: 28441057]
[129]
Jones DP, Sies H. The redox code. Antioxid Redox Signal 2015; 23(9): 734-46.
[http://dx.doi.org/10.1089/ars.2015.6247] [PMID: 25891126]
[130]
Zorov DB, Filburn CR, Klotz LO, Zweier JL, Sollott SJ. Reactive oxygen species (ROS)-induced ROS release: a new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. J Exp Med 2000; 192(7): 1001-14.
[http://dx.doi.org/10.1084/jem.192.7.1001] [PMID: 11015441]
[131]
Kuratsune H, Watanabe Y, Yamaguti K, et al. High uptake of [2-11C]acetyl-L-carnitine into the brain: a PET study. Biochem Biophys Res Commun 1997; 231(2): 488-93.
[http://dx.doi.org/10.1006/bbrc.1996.5919] [PMID: 9070306]
[132]
Aureli T, Puccetti C, Di Cocco ME, et al. Entry of [(1,2-13C2)acetyl]- l-carnitine in liver tricarboxylic acid cycle and lipogenesis. A study by 13C NMR spectroscopy in conscious, freely moving rats. Eur J Biochem 1999; 263(1): 287-91.
[http://dx.doi.org/10.1046/j.1432-1327.1999.00524.x] [PMID: 10429215]
[133]
Kidd PM. Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev 2005; 10(4): 268-93.
[PMID: 16366737]
[134]
Hota KB, Hota SK, Chaurasia OP, Singh SB. Acetyl-L-carnitine-mediated neuroprotection during hypoxia is attributed to ERK1/2-Nrf2-regulated mitochondrial biosynthesis. Hippocampus 2012; 22(4): 723-36.
[http://dx.doi.org/10.1002/hipo.20934] [PMID: 21542052]
[135]
Patel SP, Sullivan PG, Lyttle TS, Magnuson DSK, Rabchevsky AG. Acetyl-l-carnitine treatment following spinal cord injury improves mitochondrial function correlated with remarkable tissue sparing and functional recovery. Neuroscience 2012; 210: 296-307.
[http://dx.doi.org/10.1016/j.neuroscience.2012.03.006] [PMID: 22445934]
[136]
Chouhan AK, Zhang J, Zinsmaier KE, Macleod GT. Presynaptic mitochondria in functionally different motor neurons exhibit similar affinities for Ca2+ but exert little influence as Ca2+ buffers at nerve firing rates in situ. J Neurosci 2010; 30(5): 1869-81.
[http://dx.doi.org/10.1523/JNEUROSCI.4701-09.2010] [PMID: 20130196]
[137]
De Vos KJ, Chapman AL, Tennant ME, et al. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 2007; 16(22): 2720-8.
[http://dx.doi.org/10.1093/hmg/ddm226] [PMID: 17725983]
[138]
Magrané J, Sahawneh MA, Przedborski S, Estévez AG, Manfredi G. Mitochondrial dynamics and bioenergetic dysfunction is associated with synaptic alterations in mutant SOD1 motor neurons. J Neurosci 2012; 32(1): 229-42.
[http://dx.doi.org/10.1523/JNEUROSCI.1233-11.2012] [PMID: 22219285]
[139]
Pollari E, Goldsteins G, Bart G, Koistinaho J, Giniatullin R. The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis. Front Cell Neurosci 2014; 8: 131.
[http://dx.doi.org/10.3389/fncel.2014.00131] [PMID: 24860432]
[140]
Castorina M, Maria Ambrosini A, Giuliani A, Pacifici L, Teresa Ramacci M, Angelucci L. A cluster analysis study of acetyl-l-carnitine effect on NMDA receptors in aging. Exp Gerontol 1993; 28(6): 537-48.
[http://dx.doi.org/10.1016/0531-5565(93)90042-C] [PMID: 8137890]
[141]
Fariello RG, Ferraro TN, Golden GT, DeMattei M. Systemic acetyl-L-carnitine elevates nigral levels of glutathione and GABA. Life Sci 1988; 43(3): 289-92.
[http://dx.doi.org/10.1016/0024-3205(88)90319-0] [PMID: 3398700]
[142]
Nasca C, Xenos D, Barone Y, et al. L -acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci USA 2013; 110(12): 4804-9.
[http://dx.doi.org/10.1073/pnas.1216100110] [PMID: 23382250]
[143]
Smeland OB, Meisingset TW, Borges K, Sonnewald U. Chronic acetyl-l-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice. Neurochem Int 2012; 61(1): 100-7.
[http://dx.doi.org/10.1016/j.neuint.2012.04.008] [PMID: 22549035]
[144]
De Simone R, Ramacci MT, Aloe L. Effect of acetyl-L-carnitine on forebrain cholinergic neurons of developing rats. Int J Dev Neurosci 1991; 9(1): 39-46.
[http://dx.doi.org/10.1016/0736-5748(91)90071-S] [PMID: 1849696]
[145]
Traina G, Federighi G, Brunelli M, Scuri R. Cytoprotective effect of acetyl-L-carnitine evidenced by analysis of gene expression in the rat brain. Mol Neurobiol 2009; 39(2): 101-6.
[http://dx.doi.org/10.1007/s12035-009-8056-1] [PMID: 19199082]
[146]
Di Stefano G, Di Lionardo A, Galosi E, Truini A, Cruccu G. Acetyl-L-carnitine in painful peripheral neuropathy: a systematic review. J Pain Res 2019; 12: 1341-51.
[http://dx.doi.org/10.2147/JPR.S190231] [PMID: 31118753]
[147]
Wang SM, Han C, Lee SJ, Patkar AA, Masand PS, Pae CU. A review of current evidence for acetyl-l-carnitine in the treatment of depression. J Psychiatr Res 2014; 53: 30-7.
[http://dx.doi.org/10.1016/j.jpsychires.2014.02.005] [PMID: 24607292]
[148]
Notartomaso S, Mascio G, Bernabucci M, et al. Analgesia induced by the epigenetic drug, L-acetylcarnitine, outlasts the end of treatment in mouse models of chronic inflammatory and neuropathic pain. Mol Pain 2017; 13.
[http://dx.doi.org/10.1177/1744806917697009] [PMID: 28326943]
[149]
McKay Hart A, Wiberg M, Terenghi G. Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl- L -carnitine treatment. Neurosci Lett 2002; 334(3): 181-5.
[http://dx.doi.org/10.1016/S0304-3940(02)00982-5] [PMID: 12453625]
[150]
Di Cesare Mannelli L, Ghelardini C, Calvani M, et al. Protective effect of acetyl-l-carnitine on the apoptotic pathway of peripheral neuropathy. Eur J Neurosci 2007; 26(4): 820-7.
[http://dx.doi.org/10.1111/j.1460-9568.2007.05722.x] [PMID: 17714181]
[151]
Bella R, Biondi R, Raffaele R, Pennisi G. Effect of acetyl-L-carnitine on geriatric patients suffering from dysthymic disorders. Int J Clin Pharmacol Res 1990; 10(6): 355-60.
[PMID: 2099360]
[152]
Suzuki H, Hibino H, Inoue Y, Mikami K. The benefits of the concomitant use of antidepressants and acetyl-l-carnitine in the treatment of moderate depression. Asian J Psychiatr 2019; 41: 84-5.
[http://dx.doi.org/10.1016/j.ajp.2017.10.023] [PMID: 29137953]
[153]
Nasca C, Bigio B, Lee FS, et al. Acetyl- l -carnitine deficiency in patients with major depressive disorder. Proc Natl Acad Sci USA 2018; 115(34): 8627-32.
[http://dx.doi.org/10.1073/pnas.1801609115] [PMID: 30061399]
[154]
Chiechio S, Caricasole A, Barletta E, et al. L-Acetylcarnitine induces analgesia by selectively up-regulating mGlu2 metabotropic glutamate receptors. Mol Pharmacol 2002; 61(5): 989-96.
[http://dx.doi.org/10.1124/mol.61.5.989] [PMID: 11961116]
[155]
Tolu P, Masi F, Leggio B, et al. Effects of long-term acetyl-L-carnitine administration in rats: I. increased dopamine output in mesocorticolimbic areas and protection toward acute stress exposure. Neuropsychopharmacology 2002; 27(3): 410-20.
[http://dx.doi.org/10.1016/S0893-133X(02)00306-8] [PMID: 12225698]
[156]
Kobayashi S, Iwamoto M, Kon K, Waki H, Ando S, Tanaka Y. Acetyl-l-carnitine improves aged brain function. Geriatr Gerontol Int 2010; 10 (Suppl. 1): S99-S106.
[http://dx.doi.org/10.1111/j.1447-0594.2010.00595.x] [PMID: 20590847]
[157]
Kira Y, Nishikawa M, Ochi A, Sato E, Inoue M. l-Carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis. Brain Res 2006; 1070(1): 206-14.
[http://dx.doi.org/10.1016/j.brainres.2005.11.052] [PMID: 16412993]
[158]
Ishii T, Shimpo Y, Matsuoka Y, Kinoshita K. Anti-apoptotic effect of acetyl-l-carnitine and I-carnitine in primary cultured neurons. Jpn J Pharmacol 2000; 83(2): 119-24.
[http://dx.doi.org/10.1016/S0021-5198(19)30606-7] [PMID: 10928324]
[159]
Bigini P, Larini S, Pasquali C, Muzio V, Mennini T. Acetyl-l-carnitine shows neuroprotective and neurotrophic activity in primary culture of rat embryo motoneurons. Neurosci Lett 2002; 329(3): 334-8.
[http://dx.doi.org/10.1016/S0304-3940(02)00667-5] [PMID: 12183043]
[160]
Forloni G, Angeretti N, Smiroldo S. Neuroprotective activity of acetyl-L-carnitine: Studies in vitro. J Neurosci Res 1994; 37(1): 92-6.
[http://dx.doi.org/10.1002/jnr.490370112] [PMID: 7908343]
[161]
Felipo V, Grau E, Miñana MD, Grisolía S. Ammonium injection induces an N-methyl-D-aspartate receptor-mediated proteolysis of the microtubule-associated protein MAP-2. J Neurochem 1993; 60(5): 1626-30.
[http://dx.doi.org/10.1111/j.1471-4159.1993.tb13384.x] [PMID: 8473887]
[162]
Gyawali A, Hyeon SJ, Ryu H, Kang YS. The alteration of L-carnitine transport and pretreatment effect under glutamate cytotoxicity on motor neuron-like NSC-34 lines. Pharmaceutics 2021; 13(4): 551.
[http://dx.doi.org/10.3390/pharmaceutics13040551] [PMID: 33919926]
[163]
Montgomery SA, Thal LJ, Amrein R. Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer’s disease. Int Clin Psychopharmacol 2003; 18(2): 61-71.
[http://dx.doi.org/10.1097/00004850-200303000-00001] [PMID: 12598816]
[164]
Hudson SA, Tabet N. Acetyl‐l‐carnitine for dementia. Cochrane Database Syst Rev 2003; 2003(2): CD003158.
[http://dx.doi.org/10.1002/14651858.CD003158]
[165]
Pennisi M, Lanza G, Cantone M, et al. Acetyl-L-carnitine in dementia and other cognitive disorders: a critical update. Nutrients 2020; 12(5): 1389.
[http://dx.doi.org/10.3390/nu12051389] [PMID: 32408706]
[166]
Puca FM, Genco S, Specchio LM, et al. Clinical pharmacodynamics of acetyl-L-carnitine in patients with Parkinson’s disease. Int J Clin Pharmacol Res 1990; 10(1-2): 139-43.
[PMID: 2387661]
[167]
Goety CG, Tanner CM, Cohen JA, et al. L-acetyl-carnitine in Huntington’s disease: double-blind placebo controlled crossover study of drug effects on movement disorder and dementia. Mov Disord 1990; 5(3): 263-5.
[PMID: 2143808]
[168]
Beghi E, Pupillo E, Bonito V, et al. Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for ALS. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14(5-6): 397-405.
[http://dx.doi.org/10.3109/21678421.2013.764568] [PMID: 23421600]
[169]
Mancuso C, Bates TE, Butterfield DA, et al. Natural antioxidants in Alzheimer’s disease. Expert Opin Investig Drugs 2007; 16(12): 1921-31.
[http://dx.doi.org/10.1517/13543784.16.12.1921] [PMID: 18042001]
[170]
Sepand MR, Razavi-Azarkhiavi K, Omidi A, et al. Effect of acetyl-l-carnitine on antioxidant status, lipid peroxidation, and oxidative damage of arsenic in rat. Biol Trace Elem Res 2016; 171(1): 107-15.
[http://dx.doi.org/10.1007/s12011-015-0436-y] [PMID: 26349760]
[171]
Altun Z, Olgun Y, Ercetin P, et al. Protective effect of acetyl- l -carnitine against cisplatin ototoxicity: role of apoptosis-related genes and pro-inflammatory cytokines. Cell Prolif 2014; 47(1): 72-80.
[http://dx.doi.org/10.1111/cpr.12080] [PMID: 24286513]

Rights & Permissions Print Cite
Article Metrics
35
1
Wayfinder Image
© 2024 Bentham Science Publishers | Privacy Policy