N-acetylcysteine increases dopamine release and prevents the deleterious effects of 6-OHDA on the expression of VMAT2, α-synuclein, and tyrosine hydroxylase

References

• Blesa J, Trigo-Damas I, Quiroga-Varela A, et al. Oxidative stress and Parkinson’s disease. Front Neuroanat. 2015;9:91. doi: 10.3389/fnana.2015.00091
   PubMed Web of Science ®Google Scholar
• Bucher ML, Barrett CW, Moon CJ, et al. Acquired dysregulation of dopamine homeostasis reproduces features of Parkinson’s disease. NPJ Parkinson’s dis. 2020;6(1):34. doi: 10.1038/s41531-020-00134-x
   PubMed Web of Science ®Google Scholar
• Pifl C, Rajput A, Reither H, et al. Is Parkinson’s disease a vesicular dopamine storage disorder? evidence from a study in isolated synaptic vesicles of human and nonhuman primate striatum. J Neurosci. 2014;34(24):8210–8218. doi: 10.1523/jneurosci.5456-13.2014
   PubMed Web of Science ®Google Scholar
• Lohr KM, Miller GW. VMAT2 and Parkinson’s disease: harnessing the dopamine vesicle. Expert Rev Neurotherapeutics. 2014;14(10):1115–1117. doi: 10.1586/14737175.2014.960399
   PubMed Web of Science ®Google Scholar
• Taylor TN, Caudle WM, Miller GW. VMAT2-deficient mice display nigral and extranigral pathology and motor and nonmotor symptoms of Parkinson’s disease. Parkinsons Dis. 2011;2011:124165. doi: 10.4061/2011/124165
   PubMed Web of Science ®Google Scholar
• Benskey MJ, Perez RG, Manfredsson FP. The contribution of alpha synuclein to neuronal survival and function – implications for Parkinson’s disease. J Neurochem. 2016;137(3):331–359. doi: 10.1111/jnc.13570
   PubMed Web of Science ®Google Scholar
• Huang M, Wang B, Li X, et al. α-Synuclein: A Multifunctional Player in Exocytosis, Endocytosis, and Vesicle Recycling. Front Neurosci. 2019;13. doi: 10.3389/fnins.2019.00028
   Web of Science ®Google Scholar
• Stefanis L. α-Synuclein in Parkinson’s disease. Cold Spring Harb Perspect Med. 2012;2(2):a009399. doi: 10.1101/cshperspect.a009399
   PubMed Web of Science ®Google Scholar
• Manning-Bog AB, McCormack AL, Li J, et al. The herbicide paraquat causes up-regulation and aggregation of α-synuclein in mice: PARAQUAT and α-SYNUCLEIN*. J Biol Chem. 2002;277(3):1641–1644. doi: 10.1074/jbc.C100560200
   PubMed Web of Science ®Google Scholar
• Vila M, Vukosavic S, Jackson-Lewis V, et al. α-synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the Parkinsonian Toxin MPTP. J Neurochem. 2000;74(2):721–729. doi: 10.1046/j.1471-4159.2000.740721.x
   PubMed Web of Science ®Google Scholar
• Gómez-Benito M, Granado N, García-Sanz P, et al. Modeling Parkinson’s disease with the alpha-synuclein protein. Front Pharmacol. 2020;11. doi: 10.3389/fphar.2020.00356
   PubMed Web of Science ®Google Scholar
• Lundblad M, Decressac M, Mattsson B, et al. Impaired neurotransmission caused by overexpression of alpha-synuclein in nigral dopamine neurons. Proc Natl Acad Sci U S A. 2012;109(9):3213–3219. doi: 10.1073/pnas.1200575109
   PubMed Web of Science ®Google Scholar
• Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting Alpha-Synuclein as a therapy for Parkinson’s disease. Front Mol Neurosci. 2019;12. doi: 10.3389/fnmol.2019.00299
   PubMed Web of Science ®Google Scholar
• Truong JG, Rau KS, Hanson GR, et al. Pramipexole increases vesicular dopamine uptake: implications for treatment of Parkinson’s neurodegeneration. Eur J Pharmacol. 2003;474(2–3):223–226. doi: 10.1016/s0014-2999(03)02080-6
   PubMed Web of Science ®Google Scholar
• Bavarsad Shahripour R, Harrigan MR, Alexandrov AV. N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav. 2014;4(2):108–122. doi: 10.1002/brb3.208
   PubMed Web of Science ®Google Scholar
• Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. 2011;36(2):78–86. doi: 10.1503/jpn.100057
   PubMed Web of Science ®Google Scholar
• Martínez-Banaclocha MA. N-acetyl-cysteine in the treatment of Parkinson’s disease. what are we waiting for? Med Hypotheses. 2012;79(1):8–12. doi: 10.1016/j.mehy.2012.03.021
   PubMed Web of Science ®Google Scholar
• Tardiolo G, Bramanti P, Mazzon E. Overview on the effects of N-Acetylcysteine in neurodegenerative diseases. Molecules. 2018;23(12):3305. doi: 10.3390/molecules23123305
   PubMed Web of Science ®Google Scholar
• Holmay MJ, Terpstra M, Coles LD, et al. N-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases. Cli Neuropharmacol. 2013;36(4):103–106. doi: 10.1097/WNF.0b013e31829ae713
   PubMed Web of Science ®Google Scholar
• Monti DA, Zabrecky G, Kremens D, et al. N-Acetyl cysteine is associated with dopaminergic improvement in Parkinson’s disease. Clin Pharmacol Ther. 2019;106(4):884–890. doi: 10.1002/cpt.1548
   PubMed Web of Science ®Google Scholar
• Monti DA, Zabrecky G, Kremens D, et al. N-Acetyl cysteine may support dopamine neurons in Parkinson’s disease: preliminary clinical and cell line data. PloS One. 2016;11(6):e0157602–e0157602. doi: 10.1371/journal.pone.0157602
   PubMed Web of Science ®Google Scholar
• Medina S, Martínez M, Hernanz A. Antioxidants inhibit the human cortical neuron apoptosis induced by hydrogen peroxide, tumor necrosis factor alpha, dopamine and beta-amyloid peptide 1-42. Free Radic Res. 2002;36(11):1179–1184. doi: 10.1080/107157602100006445
   PubMed Web of Science ®Google Scholar
• Clark J, Clore EL, Zheng K, et al. Oral N-acetyl-cysteine attenuates loss of dopaminergic terminals in alpha-synuclein overexpressing mice. PloS One. 2010;5(8):e12333. doi: 10.1371/journal.pone.0012333
   PubMed Web of Science ®Google Scholar
• Nouraei N, Zarger L, Weilnau JN, et al. Investigation of the therapeutic potential of N-acetyl cysteine and the tools used to define nigrostriatal degeneration in vivo. Toxicol Appl Pharmacol. 2016;296:19–30. doi: 10.1016/j.taap.2016.02.010
   PubMed Web of Science ®Google Scholar
• Virel A, Dudka I, Laterveer R, et al. 1H NMR profiling of the 6-OHDA parkinsonian rat brain reveals metabolic alterations and signs of recovery after N-acetylcysteine treatment. Mol Cell Neurosci. 2019;98:131–139. doi: 10.1016/j.mcn.2019.06.003
   PubMed Web of Science ®Google Scholar
• Virel A, Johansson J, Axelsson J, et al. N-acetylcysteine decreases dopamine transporter availability in the non-lesioned striatum of the 6-OHDA hemiparkinsonian rat. Neurosci Lett. 2022;770:136420. doi: 10.1016/j.neulet.2021.136420
   PubMed Web of Science ®Google Scholar
• Martinez-Banaclocha MA. Potential Role of N-Acetyl-Cysteine in the Cysteine Proteome in Parkinson’s Disease? Clin Pharmacol Ther. 2020;107(5):1055. doi: 10.1002/cpt.1709
   PubMed Web of Science ®Google Scholar
• Martinez-Banaclocha MA. Targeting the Cysteine Redox Proteome in Parkinson’s disease: the role of glutathione precursors and beyond. Antioxidants. 2023;12(7):1373. doi: 10.3390/antiox12071373
   Web of Science ®Google Scholar
• Glinka Y, Tipton KF, Youdim MB. Nature of inhibition of mitochondrial respiratory complex I by 6-hydroxydopamine. J Neurochem. 1996;66(5):2004–2010. doi: 10.1046/j.1471-4159.1996.66052004.x
   PubMed Web of Science ®Google Scholar
• Bonilla-Porras AR, Jimenez-Del-Rio M, Velez-Pardo C. N-acetyl-cysteine blunts 6-hydroxydopamine- and l-buthionine-sulfoximine-induced apoptosis in human mesenchymal stromal cells. Mol Biol Rep. 2019;46(4):4423–4435. doi: 10.1007/s11033-019-04897-2
   PubMed Web of Science ®Google Scholar
• Chung Y, Lee J, Jung S, et al. Dysregulated autophagy contributes to caspase-dependent neuronal apoptosis. Cell Death Dis. 2018;9(12):1189. doi: 10.1038/s41419-018-1229-y
   PubMedGoogle Scholar
• Hanrott K, Gudmunsen L, O’Neill MJ, et al. 6-Hydroxydopamine-induced Apoptosis Is Mediated via Extracellular Auto-oxidation and Caspase 3-dependent Activation of Protein Kinase Cδ*. J Biol Chem. 2006;281(9):5373–5382. doi: 10.1074/jbc.M511560200
   PubMed Web of Science ®Google Scholar
• Holtz WA, Turetzky JM, Jong YJI, et al. Oxidative stress-triggered unfolded protein response is upstream of intrinsic cell death evoked by parkinsonian mimetics. Journal Of Neurochemistry. 2006;99(1):54–69. doi: 10.1111/j.1471-4159.2006.04025.x
   PubMed Web of Science ®Google Scholar
• Andrew R, Watson DG, Best SA, et al. The determination of hydroxydopamines and other trace amines in the urine of Parkinsonian patients and normal controls. Neurochem Res. 1993;18(11):1175–1177. doi: 10.1007/BF00978370
   PubMed Web of Science ®Google Scholar
• Curtius HC, Wolfensberger M, Steinmann B, et al. Mass fragmentography of dopamine and 6-hydroxydopamine: application to the determination of dopamine in human brain biopsies from the caudate nucleus. J Chromatogr A. 1974;99:529–540. doi: 10.1016/S0021-9673(00)90882-3
   PubMed Web of Science ®Google Scholar
• Borah A, Mohanakumar KP. L-DOPA induced-endogenous 6-hydroxydopamine is the cause of aggravated dopaminergic neurodegeneration in Parkinson’s disease patients. Med Hypotheses. 2012;79(2):271–273. doi: 10.1016/j.mehy.2012.05.008
   PubMed Web of Science ®Google Scholar
• Ioghen OC, Ceafalan LC, Popescu BO. SH-SY5Y cell line in vitro models for parkinson disease research—old practice for new trends. J Integr Neurosci. 2023;22(1):20. doi: 10.31083/j.jin2201020
   PubMed Web of Science ®Google Scholar
• Presgraves SP, Ahmed T, Borwege S, et al. Terminally differentiated SH-SY5Y cells provide a model system for studying neuroprotective effects of dopamine agonists. Neurotox Res. 2004;5(8):579–598. doi: 10.1007/BF03033178
   PubMed Web of Science ®Google Scholar
• Ganapathy K, Datta I, Sowmithra S, et al. Influence of 6-hydroxydopamine toxicity on alpha-Synuclein Phosphorylation, resting vesicle expression, and vesicular dopamine release. J Cell Biochem. 2016;117(12):2719–2736. doi: 10.1002/jcb.25570
   PubMed Web of Science ®Google Scholar
• Soto-Otero R, Mendez-Alvarez E, Hermida-Ameijeiras A, et al. Autoxidation and neurotoxicity of 6-hydroxydopamine in the presence of some antioxidants: potential implication in relation to the pathogenesis of Parkinson’s disease. J Neurochem. 2000;74(4):1605–1612. doi: 10.1046/j.1471-4159.2000.0741605.x
   PubMed Web of Science ®Google Scholar
• Goldstein DS, Jinsmaa Y, Sullivan P, et al. N-Acetylcysteine prevents the increase in spontaneous oxidation of dopamine during monoamine oxidase inhibition in PC12 cells. Neurochem Res. 2017;42(11):3289–3295. doi: 10.1007/s11064-017-2371-0
   PubMed Web of Science ®Google Scholar
• Bagh MB, Maiti AK, Jana S, et al. Quinone and oxyradical scavenging properties of N-acetylcysteine prevent dopamine mediated inhibition of Na+, K±ATPase and mitochondrial electron transport chain activity in rat brain: implications in the neuroprotective therapy of Parkinson’s disease. Free Radic Res. 2008;42(6):574–581. doi: 10.1080/10715760802158430
   PubMed Web of Science ®Google Scholar
• Sandilands EA, Bateman DN. Adverse reactions associated with acetylcysteine. Clin Toxicol. 2009;47(2):81–88. doi: 10.1080/15563650802665587
   PubMed Web of Science ®Google Scholar
• Garrido M, Tereshchenko Y, Zhevtsova Z, et al. Glutathione depletion and overproduction both initiate degeneration of nigral dopaminergic neurons. Acta Neuropathol. 2011;121(4):475–485. doi: 10.1007/s00401-010-0791-x
   PubMed Web of Science ®Google Scholar