The Treatment of Parkinson’s Disease with Sodium Oxybate

Mortimer      Mamelak
doi:10.2174/1874467216666221103121135
Abstract

Sodiun Oxybate (SO) has a number of attributes that may mitigate the metabolic stress on the substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons in Parkinson’s disease (PD). These neurons function at the borderline of energy sufficiency. SO is metabolized to succinate and supplies energy to the cell by generating ATP. SO is a GABAB agonist and, as such, also arrests the high energy requiring calcium pace-making activity of these neurons. In addition, blocking calcium entry impedes the synaptic release and subsequent neurotransmission of aggregated synuclein species. As DA neurons degenerate, a homeostatic failure exposes these neurons to glutamate excitotoxicity, which in turn accelerates the damage. SO inhibits the neuronal release of glutamate and blocks its agonistic actions. Most important, SO generates NADPH, the cell’s major antioxidant cofactor. Excessive free radical production within DA neurons and even more so within activated microglia are early and key features of the degenerative process that are present long before the onset of motor symptoms. NADPH maintains cell glutathione levels and alleviates oxidative stress and its toxic consequences. SO, a histone deacetylase inhibitor also suppresses the expression of microglial NADPH oxidase, the major source of free radicals in Parkinson brain. The acute clinical use of SO at night has been shown to reduce daytime sleepiness and fatigue in patients with PD. With long-term use, its capacity to supply energy to DA neurons, impede synuclein transmission, block excitotoxicity and maintain an anti-oxidative redox environment throughout the night may delay the onset of PD and slow its progress.
[1]
Mamelak, M. Parkinson’s disease, the dopaminergic neuron and gammahydroxybutyrate. Neurol. Ther.,  2018, 7(1), 5-11.
 [http://dx.doi.org/10.1007/s40120-018-0091-2] [PMID:  29368093]

[2]
Pissadaki, E.K.; Bolam, J.P. The energy cost of action potential propagation in dopamine neurons: Clues to susceptibility in Parkinson’s disease. Front. Comput. Neurosci.,  2013, 7(2), 13.
 [http://dx.doi.org/10.3389/fncom.2013.00013] [PMID:  23515615]

[3]
Surmeier, D.J.; Zampese, E. Calcium, bioenergetics, and Parkinson’s disease. Cells,  2020, 9, 1-32.

[4]
González-Rodríguez, P.; Zampese, E.; Stout, K.A.; Guzman, J.N.; Ilijic, E.; Yang, B.; Tkatch, T.; Stavarache, M.A.; Wokosin, D.L.; Gao, L.; Kaplitt, M.G.; López-Barneo, J.; Schumacker, P.T.; Surmeier, D.J. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature,  2021, 599(7886), 650-656.
 [http://dx.doi.org/10.1038/s41586-021-04059-0] [PMID:  34732887]

[5]
Pacelli, C.; Giguère, N.; Bourque, M.J.; Lévesque, M.; Slack, R.S.; Trudeau, L.É. Elevated mitochondrial bioenergetics and axonal arborization size are key contributors to the vulnerability of dopamine neurons. Curr. Biol.,  2015, 25(18), 2349-2360.
 [http://dx.doi.org/10.1016/j.cub.2015.07.050] [PMID:  26320949]

[6]
Surmeier, D.J.; Obeso, J.A.; Halliday, G.M. Selective neuronal vulnerability in Parkinson disease. Nat. Rev. Neurosci.,  2017, 18(2), 101-113.
 [http://dx.doi.org/10.1038/nrn.2016.178] [PMID:  28104909]

[7]
Guzman, J.N.; Sanchez-Padilla, J.; Wokosin, D.; Kondapalli, J.; Ilijic, E.; Schumacker, P.T.; Surmeier, D.J. Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature,  2010, 468(7324), 696-700.
 [http://dx.doi.org/10.1038/nature09536] [PMID:  21068725]

[8]
Surmeier, D.J.; Guzman, J.N.; Sanchez, J.; Schumacker, P.T. Physiological phenotype and vulnerability in Parkinson’s disease. Cold Spring Harb. Perspect. Med.,  2012, 2(7), a009290.
 [http://dx.doi.org/10.1101/cshperspect.a009290] [PMID:  22762023]

[9]
Goldstein, D.S.; Holmes, C.; Sullivan, P.; Mash, D.C.; Sidransky, E.; Stefani, A.; Kopin, I.J.; Sharabi, Y. Deficient vesicular storage: A common theme in catecholaminergic neurodegeneration. Parkinsonism Relat. Disord.,  2015, 21(9), 1013-1022.
 [http://dx.doi.org/10.1016/j.parkreldis.2015.07.009] [PMID:  26255205]

[10]
Jinsmaa, Y.; Sharabi, Y.; Sullivan, P.; Isonaka, R.; Goldstein, D.S. 3,4-Dihydroxyphenylacetaldehyde-induced protein modifications and their mitigation by N-acetylcysteine. J. Pharmacol. Exp. Ther.,  2018, 366(1), 113-124.
 [http://dx.doi.org/10.1124/jpet.118.248492] [PMID:  29700232]

[11]
Jinsmaa, Y.; Isonaka, R.; Sharabi, Y.; Goldstein, D.S. 3,4-Dihydroxyphenylacetaldehyde is more efficient than dopamine in oligomerizing and quinonizing a-synuclein. J. Pharmacol. Exp. Ther.,  2020, 372(2), 157-165.
 [http://dx.doi.org/10.1124/jpet.119.262246] [PMID:  31744850]

[12]
Hsu, L.J.; Sagara, Y.; Arroyo, A.; Rockenstein, E.; Sisk, A.; Mallory, M.; Wong, J.; Takenouchi, T.; Hashimoto, M.; Masliah, E. alpha-synuclein promotes mitochondrial deficit and oxidative stress. Am. J. Pathol.,  2000, 157(2), 401-410.
 [http://dx.doi.org/10.1016/S0002-9440(10)64553-1] [PMID:  10934145]

[13]
Burbulla, L.F.; Song, P.; Mazzulli, J.R.; Zampese, E.; Wong, Y.C.; Jeon, S.; Santos, D.P.; Blanz, J.; Obermaier, C.D.; Strojny, C.; Savas, J.N.; Kiskinis, E.; Zhuang, X.; Krüger, R.; Surmeier, D.J.; Krainc, D. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease. Science,  2017, 357(6357), 1255-1261.
 [http://dx.doi.org/10.1126/science.aam9080] [PMID:  28882997]

[14]
Emmanouilidou, E.; Minakaki, G.; Keramioti, M.V.; Xylaki, M.; Balafas, E.; Chrysanthou-Piterou, M.; Kloukina, I.; Vekrellis, K. GABA transmission via ATP-dependent K+ channels regulates α-synuclein secretion in mouse striatum. Brain,  2016, 139(3), 871-890.
 [http://dx.doi.org/10.1093/brain/awv403] [PMID:  26912647]

[15]
Foehring, R.C.; Zhang, X.F.; Lee, J.C.F.; Callaway, J.C. Endogenous calcium buffering capacity of substantia nigral dopamine neurons. J. Neurophysiol.,  2009, 102(4), 2326-2333.
 [http://dx.doi.org/10.1152/jn.00038.2009] [PMID:  19675297]

[16]
Mattson, M.P. Calcium and neurodegeneration. Aging Cell,  2007, 6(3), 337-350.
 [http://dx.doi.org/10.1111/j.1474-9726.2007.00275.x] [PMID:  17328689]

[17]
Dauer, W.; Przedborski, S. Parkinson’s disease. Neuron,  2003, 39(6), 889-909.
 [http://dx.doi.org/10.1016/S0896-6273(03)00568-3] [PMID:  12971891]

[18]
Schapira, A.H. Mitochondrial complex I deficiency in Parkinson’s disease. Adv. Neurol.,  1993, 60, 288-291.
 [PMID:  8420145]

[19]
Gao, H.M.; Liu, B.; Zhang, W.; Hong, J.S. Critical role of microglial NADPH oxidase‐derived free radicals in the in vitro MPTP model of Parkinson’s disease. FASEB J.,  2003, 17(13), 1-22.
 [http://dx.doi.org/10.1096/fj.03-0109fje] [PMID:  12897068]

[20]
Kohutnicka, M.; Lewandowska, E. Kurkowska-Jastrzębska, I.; Członkowski, A.; Członkowska, A. Microglial and astrocytic involvement in a murine model of Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology,  1998, 39(3), 167-180.
 [http://dx.doi.org/10.1016/S0162-3109(98)00022-8] [PMID:  9754903]

[21]
Doric, Z.; Nakamura, K. Principles of Parkinson’s disease disputed by model. Nature,  2021, 599, 1-2.

[22]
Nakano, M.; Imamura, H.; Sasaoka, N.; Yamamoto, M.; Uemura, N.; Shudo, T.; Fuchigami, T.; Takahashi, R.; Kakizuka, A. ATP maintenance via two types of atp regulators mitigates pathological phenotypes in mouse models of Parkinson’s disease. EBioMedicine,  2017, 22, 225-241.
 [http://dx.doi.org/10.1016/j.ebiom.2017.07.024] [PMID:  28780078]

[23]
Tieu, K. Perier, C.; Caspersen, C.; Teismann, P.; Wu, D.C.; Yan, S.D.; Naini, A.; Vila, M.; Jackson-Lewis, V.; Ramasamy, R.; Przedborski, S. D-β-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Invest.,  2003, 112(6), 892-901.
 [http://dx.doi.org/10.1172/JCI200318797] [PMID:  12975474]

[24]
Kim, W.G.; Mohney, R.P.; Wilson, B.; Jeohn, G.H.; Liu, B.; Hong, J.S. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: Role of microglia. J. Neurosci.,  2000, 20(16), 6309-6316.
 [http://dx.doi.org/10.1523/JNEUROSCI.20-16-06309.2000] [PMID:  10934283]

[25]
Gao, H.M.; Jiang, J.; Wilson, B.; Zhang, W.; Hong, J.S.; Liu, B. Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: Relevance to Parkinson’s disease. J. Neurochem.,  2002, 81(6), 1285-1297.
 [http://dx.doi.org/10.1046/j.1471-4159.2002.00928.x] [PMID:  12068076]

[26]
Qin, L.; Liu, Y.; Wang, T.; Wei, S.J.; Block, M.L.; Wilson, B.; Liu, B.; Hong, J.S. NADPH oxidase mediates lipopolysaccharide-induced neurotoxicity and proinflammatory gene expression in activated microglia. J. Biol. Chem.,  2004, 279(2), 1415-1421.
 [http://dx.doi.org/10.1074/jbc.M307657200] [PMID:  14578353]

[27]
Brown, G.C.; Borutaite, V. There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells. Mitochondrion,  2012, 12(1), 1-4.
 [http://dx.doi.org/10.1016/j.mito.2011.02.001] [PMID:  21303703]

[28]
Vilhardt, F.; Haslund-Vinding, J.; Jaquet, V.; McBean, G. Microglia antioxidant systems and redox signalling. Br. J. Pharmacol.,  2017, 174(12), 1719-1732.
 [http://dx.doi.org/10.1111/bph.13426] [PMID:  26754582]

[29]
Haslund-Vinding, J.; McBean, G.; Jaquet, V.; Vilhardt, F. NADPH oxidases in oxidant production by microglia: Activating receptors, pharmacology and association with disease. Br. J. Pharmacol.,  2017, 174(12), 1733-1749.
 [http://dx.doi.org/10.1111/bph.13425] [PMID:  26750203]

[30]
Morris, G.; Puri, B.K.; Maes, M.; Olive, L.; Berk, M.; Carvalho, A.F. The role of microglia in neuroprogressive disorders: Mechanisms and possible neurotherapeutic effects of induced ketosis. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2020, 99, 109858.
 [http://dx.doi.org/10.1016/j.pnpbp.2020.109858] [PMID:  31923453]

[31]
Ma, MW.; Wang, J.; Dhandapani, KM.; Brann, D.W. NADPH oxidase 2 regulates NLRP3 inflammasome activation in the brain after traumatic brain injury. Oxid. Med. Cell. Longev.,  2017, 2017(5), 1-18.

[32]
Sharma, N.; Nehru, B. Apocyanin, a microglial NADPH oxidase inhibitor prevents dopaminergic neuronal degeneration in lipopolysaccharide-induced parkinson’s disease model. Mol. Neurobiol.,  2016, 53(5), 3326-3337.
 [http://dx.doi.org/10.1007/s12035-015-9267-2] [PMID:  26081143]

[33]
Block, M.L.; Hong, J.S. Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism. Prog. Neurobiol.,  2005, 76(2), 77-98.
 [http://dx.doi.org/10.1016/j.pneurobio.2005.06.004] [PMID:  16081203]

[34]
Sofic, E.; Lange, K.W.; Jellinger, K.; Riederer, P. Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci. Lett.,  1992, 142(2), 128-130.
 [http://dx.doi.org/10.1016/0304-3940(92)90355-B] [PMID:  1454205]

[35]
Tanner, C.M.; Kamel, F.; Ross, G.W.; Hoppin, J.A.; Goldman, S.M.; Korell, M.; Marras, C.; Bhudhikanok, G.S.; Kasten, M.; Chade, A.R.; Comyns, K.; Richards, M.B.; Meng, C.; Priestley, B.; Fernandez, H.H.; Cambi, F.; Umbach, D.M.; Blair, A.; Sandler, D.P.; Langston, J.W. Rotenone, paraquat, and Parkinson’s disease. Environ. Health Perspect.,  2011, 119(6), 866-872.
 [http://dx.doi.org/10.1289/ehp.1002839] [PMID:  21269927]

[36]
Heinz, S.; Freyberger, A.; Lawrenz, B.; Schladt, L.; Schmuck, G.; Ellinger-Ziegelbauer, H. Mechanistic investigations of the mitochondrial complex i inhibitor rotenone in the context of pharmacological and safety evaluation. Sci. Rep.,  2017, 7, 1-13.
 [http://dx.doi.org/10.1038/srep45465]

[37]
Betarbet, R.; Sherer, T.B.; Mackenzie, G.; Garcia-osuna, M.; Panov, A.V.; Greenamyre, J.T. Chronic systemic pesticide exposure produces pd symptoms Betarbet. Nat. Neurosci.,  2000, 26, 1301-1306.
 [http://dx.doi.org/10.1038/81834] [PMID:  11100151]

[38]
Sherer, T.B.; Betarbet, R.; Kim, J.H.; Greenamyre, J.T. Selective microglial activation in the rat rotenone model of Parkinson’s disease. Neurosci. Lett.,  2003, 341(2), 87-90.
 [http://dx.doi.org/10.1016/S0304-3940(03)00172-1] [PMID:  12686372]

[39]
Sherer, T.B.; Kim, J.H.; Betarbet, R.; Greenamyre, J.T. Subcutaneous rotenone exposure causes highly selective dopaminergic degeneration and α-synuclein aggregation. Exp. Neurol.,  2003, 179(1), 9-16.
 [http://dx.doi.org/10.1006/exnr.2002.8072] [PMID:  12504863]

[40]
Sherer, T.B.; Betarbet, R.; Testa, C.M.; Seo, B.B.; Richardson, J.R.; Kim, J.H.; Miller, G.W.; Yagi, T.; Matsuno-Yagi, A.; Greenamyre, J.T. Mechanism of toxicity in rotenone models of Parkinson’s disease. J. Neurosci.,  2003, 23(34), 10756-10764.
 [http://dx.doi.org/10.1523/JNEUROSCI.23-34-10756.2003] [PMID:  14645467]

[41]
Gao, H.M.; Hong, J.S.; Zhang, W.; Liu, B. Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J. Neurosci.,  2002, 22(3), 782-790.
 [http://dx.doi.org/10.1523/JNEUROSCI.22-03-00782.2002] [PMID:  11826108]

[42]
Gao, H.M.; Liu, B.; Hong, J.S. Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J. Neurosci.,  2003, 23(15), 6181-6187.
 [http://dx.doi.org/10.1523/JNEUROSCI.23-15-06181.2003] [PMID:  12867501]

[43]
Zhou, H.; Zhang, F.; Chen, S.; Zhang, D.; Wilson, B.; Hong, J.; Gao, H.M. Rotenone activates phagocyte NADPH oxidase by binding to its membrane subunit gp91phox. Free Radic. Biol. Med.,  2012, 52(2), 303-313.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.488] [PMID:  22094225]

[44]
Zhang, W.; Wang, T.; Pei, Z.; Miller, D.S.; Wu, X.; Block, M.L.; Wilson, B.; Zhang, W.; Zhou, Y.; Hong, J.S.; Zhang, J. Aggregated α‐synuclein activates microglia: A process leading to disease progression in Parkinson’s disease. FASEB J.,  2005, 19(6), 533-542.
 [http://dx.doi.org/10.1096/fj.04-2751com] [PMID:  15791003]

[45]
Langston, J.W.; Forno, L.S.; Tetrud, J.; Reeves, A.G.; Kaplan, J.A.; Karluk, D. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann. Neurol.,  1999, 46(4), 598-605.
 [http://dx.doi.org/10.1002/1531-8249(199910)46:4<598:AID-ANA7>3.0.CO;2-F] [PMID:  10514096]

[46]
McGeer, P.L.; Schwab, C.; Parent, A.; Doudet, D. Presence of reactive microglia in monkey substantia nigra years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration. Ann. Neurol.,  2003, 54(5), 599-604.
 [http://dx.doi.org/10.1002/ana.10728] [PMID:  14595649]

[47]
Wu, D.C.; Teismann, P.; Tieu, K.; Vila, M.; Jackson-Lewis, V.; Ischiropoulos, H.; Przedborski, S. NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson’s disease. Proc. Natl. Acad. Sci.,  2003, 100(10), 6145-6150.
 [http://dx.doi.org/10.1073/pnas.0937239100] [PMID:  12721370]

[48]
Stokholm, M.G.; Iranzo, A.; Østergaard, K.; Serradell, M.; Otto, M.; Svendsen, K.B.; Garrido, A.; Vilas, D.; Borghammer, P.; Santamaria, J.; Møller, A.; Gaig, C.; Brooks, D.J.; Tolosa, E.; Pavese, N. Assessment of neuroinflammation in patients with idiopathic rapid-eye-movement sleep behaviour disorder: A case-control study. Lancet Neurol.,  2017, 16(10), 789-796.
 [http://dx.doi.org/10.1016/S1474-4422(17)30173-4] [PMID:  28684245]

[49]
Ouchi, Y.; Yoshikawa, E.; Sekine, Y.; Futatsubashi, M.; Kanno, T.; Ogusu, T.; Torizuka, T. Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann. Neurol.,  2005, 57(2), 168-175.
 [http://dx.doi.org/10.1002/ana.20338] [PMID:  15668962]

[50]
Lavisse, S.; Goutal, S.; Wimberley, C.; Tonietto, M.; Bottlaender, M.; Gervais, P. Increased microglial activation in patients with Parkinson disease using [18F]-DPA714 TSPO PET imaging. Park Relat. Disord.,  2021, 82, 29-36.

[51]
Imamura, K.; Hishikawa, N.; Sawada, M.; Nagatsu, T.; Yoshida, M.; Hashizume, Y. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol.,  2003, 106(6), 518-526.
 [http://dx.doi.org/10.1007/s00401-003-0766-2] [PMID:  14513261]

[52]
Chinta, S.J.; Andersen, J.K. Reversible inhibition of mitochondrial complex I activity following chronic dopaminergic glutathione depletion in vitro: Implications for Parkinson’s disease. Free Radic. Biol. Med.,  2006, 41(9), 1442-1448.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2006.08.002] [PMID:  17023271]

[53]
Zhou, J.; Zhu, Z.; Wu, F.; Zhou, Y.; Sheng, R.; Wu, J.; Qin, Z. NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation. Acta Pharmacol. Sin.,  2019, 40(2), 180-191.
 [http://dx.doi.org/10.1038/s41401-018-0003-0] [PMID:  29769744]

[54]
Li, M.; Zhou, Z.P.; Sun, M.; Cao, L.; Chen, J.; Qin, Y.Y.; Gu, J.H.; Han, F.; Sheng, R.; Wu, J.C.; Ding, Y.; Qin, Z.H. Reduced nicotinamide adenine dinucleotide phosphate, a pentose phosphate pathway product, might be a novel drug candidate for ischemic stroke. Stroke,  2016, 47(1), 187-195.
 [http://dx.doi.org/10.1161/STROKEAHA.115.009687] [PMID:  26564104]

[55]
Qin, Y.Y.; Li, M.; Feng, X.; Wang, J.; Cao, L.; Shen, X.K.; Chen, J.; Sun, M.; Sheng, R.; Han, F.; Qin, Z.H. Combined NADPH and the NOX inhibitor apocynin provides greater anti-inflammatory and neuroprotective effects in a mouse model of stroke. Free Radic. Biol. Med.,  2017, 104(1), 333-345.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2017.01.034] [PMID:  28132925]

[56]
Dunn, L.; Fairfield, V.; Daham, S.; Bolaños, J.; Heales, S. Pentose-phosphate pathway disruption in the pathogenesis of Parkinson’s disease. Transl. Neurosci.,  2014, 5(3), 179-184.
 [http://dx.doi.org/10.2478/s13380-014-0221-y]

[57]
Herken, H. Neurotoxin-induced impairment of biopterin synthesis and function: Initial stage of a Parkinson-like dopamine deficiency syndrome. Neurochem. Int.,  1990, 17(2), 223-238.
 [http://dx.doi.org/10.1016/0197-0186(90)90145-J] [PMID:  20504623]

[58]
Yang, J.; Kim, M.J.; Yoon, W.; Kim, E.Y.; Kim, H.; Lee, Y.; Min, B.; Kang, K.S.; Son, J.H.; Park, H.T.; Chung, J.; Koh, H. Isocitrate protects DJ-1 null dopaminergic cells from oxidative stress through NADP+-dependent isocitrate dehydrogenase (IDH). PLoS Genet.,  2017, 13(8), e1006975.
 [http://dx.doi.org/10.1371/journal.pgen.1006975] [PMID:  28827794]

[59]
Kim, H.; Kim, S.H.; Cha, H.; Kim, S.R.; Lee, J.H.; Park, J.W. IDH2 deficiency promotes mitochondrial dysfunction and dopaminergic neurotoxicity: Implications for Parkinson’s disease. Free Radic. Res.,  2016, 50(8), 853-860.
 [http://dx.doi.org/10.1080/10715762.2016.1185519] [PMID:  27142242]

[60]
Almikhlafi, M.A.; Stauch, K.L.; Villeneuve, L.M.; Purnell, P.R.; Lamberty, B.G.; Fox, H.S. Deletion of DJ-1 in rats affects protein abundance and mitochondrial function at the synapse. Sci. Rep.,  2020, 10(1), 13719.
 [http://dx.doi.org/10.1038/s41598-020-70486-0] [PMID:  32792613]

[61]
Choi, J.; Sullards, M.C.; Olzmann, J.A.; Rees, H.D.; Weintraub, S.T.; Bostwick, D.E.; Gearing, M.; Levey, A.I.; Chin, L.S.; Li, L. Oxidative damage of DJ-1 is linked to sporadic Parkinson and Alzheimer diseases. J. Biol. Chem.,  2006, 281(16), 10816-10824.
 [http://dx.doi.org/10.1074/jbc.M509079200] [PMID:  16517609]

[62]
Repici, M.; Giorgini, F. DJ-1 in Parkinson’s disease: Clinical insights and therapeutic perspectives. J. Clin. Med.,  2019, 8(9), 1377.
 [http://dx.doi.org/10.3390/jcm8091377] [PMID:  31484320]

[63]
Laborit, H. Sodium 4-hydroxybutyrate. Int. J. Neuropharmacol.,  1964, 3(4), 433-IN8.
 [http://dx.doi.org/10.1016/0028-3908(64)90074-7] [PMID:  14334876]

[64]
Taberner, P.V.; Rick, J.T.; Kerkut, G.A. The action of gamma-hydroxybutyric acid on cerebral glucose metabolism. J. Neurochem.,  1972, 19(2), 245-254.
 [http://dx.doi.org/10.1111/j.1471-4159.1972.tb01334.x] [PMID:  5010074]

[65]
Ottani, A.; Saltini, S.; Bartiromo, M.; Zaffe, D.; Renzo Botticelli, A.; Ferrari, A.; Bertolini, A.; Genedani, S. Effect of γ-hydroxybutyrate in two rat models of focal cerebral damage. Brain Res.,  2003, 986(1-2), 181-190.
 [http://dx.doi.org/10.1016/S0006-8993(03)03252-9] [PMID:  12965243]

[66]
Yung, J.H.M.; Yeung, L.S.N.; Ivovic, A.; Tan, Y.F.; Jentz, E.M.; Batchuluun, B.; Gohil, H.; Wheeler, M.B.; Joseph, J.W.; Giacca, A.; Mamelak, M. Prevention of lipotoxicity in pancreatic islets with gammahydroxybutyrate. Cells,  2022, 11(3), 545.
 [http://dx.doi.org/10.3390/cells11030545] [PMID:  35159354]

[67]
Monti, D.A. Zabrecky, G.; Kremens, D.; Liang, T.W.; Wintering, N.A.; Bazzan, A.J.; Zhong, L.; Bowens, B.K.; Chervoneva, I.; Intenzo, C.; Newberg, A.B. N‐acetyl cysteine is associated with dopaminergic improvement in Parkinson’s disease. Clin. Pharmacol. Ther.,  2019, 106(4), 884-890.
 [http://dx.doi.org/10.1002/cpt.1548] [PMID:  31206613]

[68]
Zhou, Z.D.; Lim, T.M. Dopamine (DA) induced irreversible proteasome inhibition via DA derived quinones. Free Radic. Res.,  2009, 43(4), 417-430.
 [http://dx.doi.org/10.1080/10715760902801533] [PMID:  19291591]

[69]
Berman, S.B.; Hastings, T.G. Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: Implications for Parkinson’s disease. J. Neurochem.,  1999, 73(3), 1127-1137.
 [http://dx.doi.org/10.1046/j.1471-4159.1999.0731127.x] [PMID:  10461904]

[70]
Gautam, A.H.; Zeevalk, G.D. Characterization of reduced and oxidized dopamine and 3,4-dihydrophenylacetic acid, on brain mitochondrial electron transport chain activities. Biochim. Biophys. Acta Bioenerg.,  2011, 1807(7), 819-828.
 [http://dx.doi.org/10.1016/j.bbabio.2011.03.013] [PMID:  21463600]

[71]
Vermeer, L.M.M.; Florang, V.R.; Doorn, J.A. Catechol and aldehyde moieties of 3,4-dihydroxyphenylacetaldehyde contribute to tyrosine hydroxylase inhibition and neurotoxicity. Brain Res.,  2012, 1474, 100-109.
 [http://dx.doi.org/10.1016/j.brainres.2012.07.048] [PMID:  22877852]

[72]
Coles, L.D.; Tuite, P.J.; Öz, G.; Mishra, U.R.; Kartha, R.V.; Sullivan, K.M.; Cloyd, J.C.; Terpstra, M. Repeated-dose Oral N-acetylcysteine in parkinson’s disease: Pharmacokinetics and effect on brain glutathione and oxidative stress. J. Clin. Pharmacol.,  2018, 58(2), 158-167.
 [http://dx.doi.org/10.1002/jcph.1008] [PMID:  28940353]

[73]
Goldstein, D.S.; Sullivan, P.; Cooney, A.; Jinsmaa, Y.; Sullivan, R.; Gross, D.J.; Holmes, C.; Kopin, I.J.; Sharabi, Y. Vesicular uptake blockade generates the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde in PC12 cells: Relevance to the pathogenesis of Parkinson’s disease. J. Neurochem.,  2012, 123(6), 932-943.
 [http://dx.doi.org/10.1111/j.1471-4159.2012.07924.x] [PMID:  22906103]

[74]
Pifl, C.; Rajput, A.; Reither, H.; Blesa, J.; Cavada, C.; Obeso, J.A.; Rajput, A.H.; Hornykiewicz, O. 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.
 [http://dx.doi.org/10.1523/JNEUROSCI.5456-13.2014] [PMID:  24920625]

[75]
Plotegher, N.; Berti, G.; Ferrari, E.; Tessari, I.; Zanetti, M.; Lunelli, L.; Greggio, E.; Bisaglia, M.; Veronesi, M.; Girotto, S.; Dalla Serra, M.; Perego, C.; Casella, L.; Bubacco, L. DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function. Sci. Rep.,  2017, 7(1), 40699.
 [http://dx.doi.org/10.1038/srep40699] [PMID:  28084443]

[76]
Yosunkaya, A.; Ak, A. Barişkaner, H.; Ustün, M.E.; Tuncer, S.; Gürbilek, M. Effect of gamma-hydroxybutyric acid on lipid peroxidation and tissue lactate level in experimental head trauma. J. Trauma,  2004, 56(3), 585-590.
 [http://dx.doi.org/10.1097/01.TA.0000058119.60074.25] [PMID:  15128130]

[77]
Morawska, MM; Moreira, C; Ginde, V; Valko, P; Imbach, L; Masneuf, S Slow-wave energy enhancement associated with reduced synucleinopathy in Murine model of Parkinson’s disease.Sleep Med,,  2017, 40(2017), e230.
 [http://dx.doi.org/10.1016/j.sleep.2017.11.672]

[78]
Morawska, M.M.; Moreira, C.G.; Ginde, V.R.; Valko, P.O.; Weiss, T.; Büchele, F.; Imbach, L.L.; Masneuf, S.; Kollarik, S.; Prymaczok, N.; Gerez, J.A.; Riek, R.; Baumann, C.R.; Noain, D. Slow-wave sleep affects synucleinopathy and regulates proteostatic processes in mouse models of Parkinson’s disease. Sci. Transl. Med.,  2021, 13(623), eabe7099.
 [http://dx.doi.org/10.1126/scitranslmed.abe7099] [PMID:  34878820]

[79]
Ondo, W.G.; Perkins, T.; Swick, T.; Hull, K.L., Jr; Jiminez, J. Sodium oxybate for excessive daytime sleepiness in Parkinson’s disease: An open label polysomnigraphic study. Arch. Neurol.,  2008, 65(10), 1337-1340.
 [http://dx.doi.org/10.1001/archneur.65.10.1337] [PMID:  18852348]

[80]
Büchele, F.; Hackius, M.; Schreglmann, S.R.; Omlor, W.; Werth, E.; Maric, A.; Imbach, L.L.; Hägele-Link, S.; Waldvogel, D.; Baumann, C.R. Sodium oxybate for excessive daytime sleepiness and sleep disturbance in Parkinson disease: A randomized clinical trial. JAMA Neurol.,  2018, 75(1), 114-118.
 [http://dx.doi.org/10.1001/jamaneurol.2017.3171] [PMID:  29114733]

[81]
Schreiner, S.J.; Imbach, L.L.; Werth, E.; Poryazova, R.; Baumann-Vogel, H.; Valko, P.O.; Murer, T.; Noain, D.; Baumann, C.R. Slow‐wave sleep and motor progression in Parkinson disease. Ann. Neurol.,  2019, 85(5), 765-770.
 [http://dx.doi.org/10.1002/ana.25459] [PMID:  30887557]

[82]
Mamelak, M. Sleep, narcolepsy, and sodium oxybate. Curr. Neuropharmacol.,  2022, 20(2), 272-291.
 [http://dx.doi.org/10.2174/1570159X19666210407151227] [PMID:  33827411]

[83]
Kaufman, E.E.; Nelson, T. An overview of γ-hydroxybutyrate catabolism: The role of the cytosolic NADP+-dependent oxidoreductase EC 1.1.1.19 and of a mitochondrial hydroxyacid-oxoacid transhydrogenase in the initial, rate-limiting step in this pathway. Neurochem. Res.,  1991, 16, 965-974.

[84]
Bukato, G. Kochan, Z.; Świerczyński, J. Different regulatory properties of the cytosolic and mitochondrial forms of malic enzyme isolated from human brain. Int. J. Biochem. Cell Biol.,  1995, 27(10), 1003-1008.
 [http://dx.doi.org/10.1016/1357-2725(95)00080-9] [PMID:  7496989]

[85]
Vogel, R.; Wiesinger, H.; Hamprecht, B.; Dringen, R. The regeneration of reduced glutathione in rat forebrain mitochondria identifies metabolic pathways providing the NADPH required. Neurosci. Lett.,  1999, 275(2), 97-100.
 [http://dx.doi.org/10.1016/S0304-3940(99)00748-X] [PMID:  10568508]

[86]
Reimund, E. The free radical flux theory of sleep. Med. Hypotheses,  1994, 43(4), 231-233.
 [http://dx.doi.org/10.1016/0306-9877(94)90071-X] [PMID:  7838006]

[87]
Aalling, N.N.; Nedergaard, M.; DiNuzzo, M. Cerebral metabolic changes during sleep. Curr. Neurol. Neurosci. Rep.,  2018, 18(9), 57.
 [http://dx.doi.org/10.1007/s11910-018-0868-9] [PMID:  30014344]

[88]
Maquet, P.; Dive, D.; Salmon, E.; Sadzot, B.; Franco, G.; Poirrier, R.; von Frenckell, R.; Franck, G. Cerebral glucose utilization during sleep-wake cycle in man determined by positron emission tomography and [18F]2-fluoro-2-deoxy-d-glucose method. Brain Res.,  1990, 513(1), 136-143.
 [http://dx.doi.org/10.1016/0006-8993(90)91099-3] [PMID:  2350676]

[89]
Madsen, P.L.; Schmidt, J.F.; Wildschiødtz, G.; Friberg, L.; Holm, S.; Vorstrup, S.; Lassen, N.A. Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep. J. Appl. Physiol.,  1991, 70(6), 2597-2601.
 [http://dx.doi.org/10.1152/jappl.1991.70.6.2597] [PMID:  1885454]

[90]
Caporale, A.; Lee, H.; Lei, H.; Rao, H.; Langham, M.C.; Detre, J.A. Cerebral metabolic rate of oxygen during transition from wakefulness to sleep measured with high temporal resolution OxFlow MRI with concurrent EEG. J. Cereb. Blood Flow Metab.,  2021, 41(4), 780-792.
 [PMID:  32538283]

[91]
Mackiewicz, M.; Shockley, K.R.; Romer, M.A.; Galante, R.J.; Zimmerman, J.E.; Naidoo, N.; Baldwin, D.A.; Jensen, S.T.; Churchill, G.A.; Pack, A.I. Macromolecule biosynthesis: A key function of sleep. Physiol. Genomics,  2007, 31(3), 441-457.
 [http://dx.doi.org/10.1152/physiolgenomics.00275.2006] [PMID:  17698924]

[92]
Atrooz, F.; Salim, S. Sleep deprivation, oxidative stress and inflammation. Adv. Protein Chem. Struct. Biol.,  2020, 119, 309-336.
 [http://dx.doi.org/10.1016/bs.apcsb.2019.03.001] [PMID:  31997771]

[93]
Villafuerte, G.; Miguel-Puga, A.; Murillo, E.; Machado, S.; Manjarrez, E.; Arias-Carrión, O. Sleep deprivation and oxidative stress in animal models: A systematic review. Oxid. Med. Cell. Longev.,  2015, 2015, 234952.
 [http://dx.doi.org/10.1155/2015/234952]

[94]
Harkness, J.H.; Bushana, P.N.; Todd, R.P.; Clegern, W.C.; Sorg, B.A.; Wisor, J.P. Sleep disruption elevates oxidative stress in parvalbumin-positive cells of the rat cerebral cortex. Sleep,  2019, 42(1), 1-15.
 [http://dx.doi.org/10.1093/sleep/zsy201] [PMID:  30371896]

[95]
Pimentel, D.; Donlea, J.M.; Talbot, C.B.; Song, S.M.; Thurston, A.J.F.; Miesenböck, G. Operation of a homeostatic sleep switch. Nature,  2016, 536(7616), 333-337. Available from: http://www.nature.com/authors/editorial_policies/license.html#terms
 [http://dx.doi.org/10.1038/nature19055] [PMID:  27487216]

[96]
Kempf, A.; Song, S.M.; Talbot, C.B.; Miesenböck, G. A potassium channel β-subunit couples mitochondrial electron transport to sleep. Nature,  2019, 568(7751), 230-234.
 [http://dx.doi.org/10.1038/s41586-019-1034-5] [PMID:  30894743]

[97]
Hill, V.M.; O’Connor, R.M.; Sissoko, G.B.; Irobunda, I.S.; Leong, S.; Canman, J.C.; Stavropoulos, N.; Shirasu-Hiza, M. A bidirectional relationship between sleep and oxidative stress in Drosophila. PLoS Biol.,  2018, 16(7), e2005206.
 [http://dx.doi.org/10.1371/journal.pbio.2005206] [PMID:  30001323]

[98]
Ikeda, M.; Ikeda-Sagara, M.; Okada, T.; Clement, P.; Urade, Y.; Nagai, T.; Sugiyama, T.; Yoshioka, T.; Honda, K.; Inoué, S. Brain oxidation is an initial process in sleep induction. Neuroscience,  2005, 130(4), 1029-1040.
 [http://dx.doi.org/10.1016/j.neuroscience.2004.09.057] [PMID:  15652998]

[99]
Crunelli, V.; Leresche, N. Unravelling the brain targets of gamma-hydroxybutyric acid. Curr. Opin. Pharmacol.,  2006, 6(1), 44-52.

[100]
Haller, C.; Mende, M.; Schuier, F.; Schuh, R.; Schröck, H.; Kuschinsky, W. Effect of γ-hydroxybutyrate on local and global glucose metabolism in the anesthetized cat brain. J. Cereb. Blood Flow Metab.,  1990, 10(4), 493-498.
 [http://dx.doi.org/10.1038/jcbfm.1990.91] [PMID:  2347880]

[101]
Black, J.; Swick, T.; Bogan, R.; Lai, C.; Carter, L.P. Impact of sodium oxybate, modafinil, and combination treatment on excessive daytime sleepiness in patients who have narcolepsy with or without cataplexy. Sleep Med.,  2016, 24, 57-62.
 [http://dx.doi.org/10.1016/j.sleep.2016.07.010] [PMID:  27810187]

[102]
Plazzi, G.; Pizza, F.; Vandi, S.; Aricò, D.; Bruni, O.; Dauvilliers, Y.; Ferri, R. Impact of acute administration of sodium oxybate on nocturnal sleep polysomnography and on multiple sleep latency test in narcolepsy with cataplexy. Sleep Med.,  2014, 15(9), 1046-1054.
 [http://dx.doi.org/10.1016/j.sleep.2014.04.020] [PMID:  25087195]

[103]
van Schie, M.K.M.; Werth, E.; Lammers, G.J.; Overeem, S.; Baumann, C.R.; Fronczek, R. Improved vigilance after sodium oxybate treatment in narcolepsy: a comparison between in-field and in-laboratory measurements. J. Sleep Res.,  2016, 25(4), 486-496.
 [http://dx.doi.org/10.1111/jsr.12386] [PMID:  26909768]

[104]
Black, J.; Houghton, W.C. Sodium oxybate improves excessive daytime sleepiness in narcolepsy. Sleep,  2006, 29(7), 939-946.
 [http://dx.doi.org/10.1093/sleep/29.7.939] [PMID:  16895262]

[105]
Abad, V.C. An evaluation of sodium oxybate as a treatment option for narcolepsy. Expert Opin. Pharmacother.,  2019, 20(10), 1189-1199.
 [http://dx.doi.org/10.1080/14656566.2019.1617273] [PMID:  31136215]

[106]
Boscolo-Berto, R.; Viel, G.; Montagnese, S.; Raduazzo, D.I.; Ferrara, S.D.; Dauvilliers, Y. Narcolepsy and effectiveness of gamma-hydroxybutyrate (GHB): A systematic review and meta-analysis of randomized controlled trials. Sleep Med. Rev.,  2012, 16(5), 431-443.
 [http://dx.doi.org/10.1016/j.smrv.2011.09.001] [PMID:  22055895]

[107]
Mamelak, M.; Black, J.; Montplaisir, J.; Ristanovic, R. A pilot study on the effects of sodium oxybate on sleep architecture and daytime alertness in narcolepsy. Sleep,  2004, 27(7), 1327-1334.
 [http://dx.doi.org/10.1093/sleep/27.7.1327] [PMID:  15586785]

[108]
Junnarkar, G.; Allphin, C.; Profant, J.; Steininger, T.L.; Chen, C.; Zomorodi, K.; Skowronski, R.; Black, J. Development of a lower-sodium oxybate formulation for the treatment of patients with narcolepsy and idiopathic hypersomnia. Expert Opin. Drug Discov.,  2022, 17(2), 109-119.
 [http://dx.doi.org/10.1080/17460441.2022.1999226] [PMID:  34818123]

[109]
Bolam, J.P.; Pissadaki, E.K. Living on the edge with too many mouths to feed: Why dopamine neurons die. Mov. Disord.,  2012, 27(12), 1478-1483.
 [http://dx.doi.org/10.1002/mds.25135] [PMID:  23008164]

[110]
Hunn, B.H.M.; Cragg, S.J.; Bolam, J.P.; Spillantini, M.G.; Wade-Martins, R. Impaired intracellular trafficking defines early Parkinson’s disease. Trends Neurosci.,  2015, 38(3), 178-188.
 [http://dx.doi.org/10.1016/j.tins.2014.12.009] [PMID:  25639775]

[111]
Muddapu, V.R.; Chakravarthy, V.S. Influence of energy deficiency on the subcellular processes of Substantia Nigra Pars Compacta cell for understanding Parkinsonian neurodegeneration. In: Scientific Reports; Nature Publishing Group: UK, 2021; pp. 1-36.
 [http://dx.doi.org/10.1038/s41598-021-81185-9]

[112]
Rodriguez, M.C.; Obeso, J.A.; Olanow, C.W. Subthalamic nucleus-mediated excitotoxicity in parkinson’s disease: A target for neuroprotection. Ann. Neurol.,  1998, 44(S1), S175-S188.
 [http://dx.doi.org/10.1002/ana.410440726] [PMID:  9749591]

[113]
Milber, J.M.; Noorigian, J.V.; Morley, J.F.; Petrovitch, H.; White, L.; Ross, G.W. Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease.,  2012, 79(24), 2307-2314.
 [http://dx.doi.org/10.1212/WNL.0b013e318278fe32]

[114]
Beach, T.G.; Adler, C.H.; Sue, L.I.; Peirce, J.B.; Bachalakuri, J.; Dalsing-Hernandez, J.E.; Lue, L.F.; Caviness, J.N.; Connor, D.J.; Sabbagh, M.N.; Walker, D.G. Reduced striatal tyrosine hydroxylase in incidental Lewy body disease. Acta Neuropathol.,  2008, 115(4), 445-451.
 [http://dx.doi.org/10.1007/s00401-007-0313-7] [PMID:  17985144]

[115]
Iacono, D.; Geraci-Erck, M.; Rabin, M.L.; Adler, C.H.; Serrano, G.; Beach, T.G.; Kurlan, R. Parkinson disease and incidental Lewy body disease. Neurology,  2015, 85(19), 1670-1679.
 [http://dx.doi.org/10.1212/WNL.0000000000002102] [PMID:  26468408]

[116]
Adler, C.H.; Beach, T.G. Neuropathological basis of nonmotor manifestations of Parkinson’s disease. Mov. Disord.,  2016, 31(8), 1114-1119.
 [http://dx.doi.org/10.1002/mds.26605] [PMID:  27030013]

[117]
Ashraf, A.; Clark, M.; So, P.W. The aging of iron man. Front. Aging Neurosci.,  2018, 10(3), 65.
 [http://dx.doi.org/10.3389/fnagi.2018.00065] [PMID:  29593525]

[118]
Ionescu-Tucker, A.; Cotman, C.W. Emerging roles of oxidative stress in brain aging and Alzheimer’s disease. Neurobiol. Aging,  2021, 107, 86-95.
 [http://dx.doi.org/10.1016/j.neurobiolaging.2021.07.014] [PMID:  34416493]

[119]
Niraula, A.; Sheridan, J.F.; Godbout, J.P. Microglia priming with aging and stress. Neuropsychopharmacology,  2017, 42(1), 318-333.
 [http://dx.doi.org/10.1038/npp.2016.185] [PMID:  27604565]

[120]
Primiani, C.T.; Ryan, V.H.; Rao, J.S.; Cam, M.C.; Ahn, K.; Modi, H.R.; Rapoport, S.I. Coordinated gene expression of neuroinflammatory and cell signaling markers in dorsolateral prefrontal cortex during human brain development and aging. PLoS One,  2014, 9(10), e110972.
 [http://dx.doi.org/10.1371/journal.pone.0110972] [PMID:  25329999]

[121]
Kiffin, R.; Kaushik, S.; Zeng, M.; Bandyopadhyay, U.; Zhang, C.; Massey, A.C.; Martinez-Vicente, M.; Cuervo, A.M. Altered dynamics of the lysosomal receptor for chaperone-mediated autophagy with age. J. Cell Sci.,  2007, 120(5), 782-791.
 [http://dx.doi.org/10.1242/jcs.001073] [PMID:  17284523]

[122]
Reeve, A.; Simcox, E.; Turnbull, D. Ageing and Parkinson’s disease: Why is advancing age the biggest risk factor? Ageing Res. Rev.,  2014, 14(1), 19-30.
 [http://dx.doi.org/10.1016/j.arr.2014.01.004] [PMID:  24503004]

[123]
Gan-Or, Z.; Dion, P.A.; Rouleau, G.A. Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease. Autophagy,  2015, 11(9), 1443-1457.
 [http://dx.doi.org/10.1080/15548627.2015.1067364] [PMID:  26207393]

[124]
Kalinderi, K.; Bostantjopoulou, S.; Fidani, L. The genetic background of Parkinson’s disease: Current progress and future prospects. Acta Neurol. Scand.,  2016, 134(5), 314-326.
 [http://dx.doi.org/10.1111/ane.12563] [PMID:  26869347]

[125]
Malpartida, A.B.; Williamson, M.; Narendra, D.P.; Wade-Martins, R.; Ryan, B.J. Mitochondrial dysfunction and mitophagy in parkinson’s disease: From mechanism to therapy. Trends Biochem. Sci.,  2021, 46(4), 329-343.
 [http://dx.doi.org/10.1016/j.tibs.2020.11.007] [PMID:  33323315]

[126]
Ryan, B.J.; Hoek, S.; Fon, E.A.; Wade-Martins, R. Mitochondrial dysfunction and mitophagy in Parkinson’s: From familial to sporadic disease. Trends Biochem. Sci.,  2015, 40(4), 200-210.
 [http://dx.doi.org/10.1016/j.tibs.2015.02.003] [PMID:  25757399]

[127]
Tagliaferro, P.; Burke, R.E. Retrograde axonal degeneration in Parkinson disease. J. Parkinsons Dis.,  2016, 6(1), 1-15.
 [http://dx.doi.org/10.3233/JPD-150769] [PMID:  27003783]

[128]
Arnulf, I. REM sleep behavior disorder: Motor manifestations and pathophysiology. Mov. Disord.,  2012, 27(6), 677-689.
 [http://dx.doi.org/10.1002/mds.24957] [PMID:  22447623]

[129]
Iranzo, A.; Tolosa, E.; Gelpi, E.; Molinuevo, J.L.; Valldeoriola, F.; Serradell, M.; Sanchez-Valle, R.; Vilaseca, I.; Lomeña, F.; Vilas, D. LLadó, A.; Gaig, C.; Santamaria, J. Neurodegenerative disease status and post-mortem pathology in idiopathic rapid-eye-movement sleep behaviour disorder: An observational cohort study. Lancet Neurol.,  2013, 12(5), 443-453.
 [http://dx.doi.org/10.1016/S1474-4422(13)70056-5] [PMID:  23562390]

[130]
Iranzo, A.; Valldeoriola, F.; Lomeña, F.; Molinuevo, J.L.; Serradell, M.; Salamero, M.; Cot, A.; Ros, D.; Pavía, J.; Santamaria, J.; Tolosa, E. Serial dopamine transporter imaging of nigrostriatal function in patients with idiopathic rapid-eye-movement sleep behaviour disorder: A prospective study. Lancet Neurol.,  2011, 10(9), 797-805.
 [http://dx.doi.org/10.1016/S1474-4422(11)70152-1] [PMID:  21802993]

[131]
Beauchamp, L.C.; Villemagne, V.L.; Finkelstein, D.I.; Doré, V.; Bush, A.I.; Barnham, K.J.; Rowe, C.C. Reduced striatal vesicular monoamine transporter 2 in REM sleep behavior disorder: Imaging prodromal parkinsonism. Sci. Rep.,  2020, 10(1), 17631.
 [http://dx.doi.org/10.1038/s41598-020-74495-x] [PMID:  33097764]

[132]
Sun, J.; Lai, Z.; Ma, J.; Gao, L.; Chen, M.; Chen, J.; Fang, J.; Fan, Y.; Bao, Y.; Zhang, D.; Chan, P.; Yang, Q.; Ye, C.; Wu, T.; Ma, T. Quantitative evaluation of iron content in idiopathic rapid eye movement sleep behavior disorder. Mov. Disord.,  2020, 35(3), 478-485.
 [http://dx.doi.org/10.1002/mds.27929] [PMID:  31846123]

[133]
Takahashi, H.; Kashiwagi, N.; Arisawa, A.; Matsuo, C.; Kato, H.; Adachi, H. Imaging of the nigrostriatal system for evaluating the preclinical phase of Parkinson’s disease development: The utility of neuromelanin, diffusion MRI, and DAT-SPECT. Br. J. Radiol.,  2021, 95, 1130.
 [PMID:  34808066]

[134]
Bae, Y.J.; Kim, J.M.; Sohn, C.H.; Choi, J.H.; Choi, B.S.; Song, Y.S.; Nam, Y.; Cho, S.J.; Jeon, B.; Kim, J.H. Imaging the substantia nigra in Parkinson disease and other Parkinsonian syndromes. Radiology,  2021, 300(2), 260-278.
 [http://dx.doi.org/10.1148/radiol.2021203341] [PMID:  34100679]

[135]
Bae, Y.J.; Kim, J.M.; Kim, K.J.; Kim, E.; Park, H.S.; Kang, S.Y.; Yoon, I.Y.; Lee, J.Y.; Jeon, B.; Kim, S.E. Loss of Substantia Nigra Hyperintensity at 3.0-T MR Imaging in Idiopathic REM Sleep Behavior Disorder: Comparison with 123 I-FP-CIT SPECT. Radiology,  2018, 287(1), 285-293.
 [http://dx.doi.org/10.1148/radiol.2017162486] [PMID:  29232183]

[136]
De Marzi, R.; Seppi, K.; Högl, B.; Müller, C.; Scherfler, C.; Stefani, A.; Iranzo, A.; Tolosa, E.; Santamarìa, J.; Gizewski, E.; Schocke, M.; Skalla, E.; Kremser, C.; Poewe, W. Loss of dorsolateral nigral hyperintensity on 3.0 tesla susceptibility-weighted imaging in idiopathic rapid eye movement sleep behavior disorder. Ann. Neurol.,  2016, 79(6), 1026-1030.
 [http://dx.doi.org/10.1002/ana.24646] [PMID:  27016314]

[137]
Barber, T.R.; Griffanti, L.; Bradley, K.M.; McGowan, D.R.; Lo, C.; Mackay, C.E.; Hu, M.T.; Klein, J.C. Nigrosome 1 imaging in REM sleep behavior disorder and its association with dopaminergic decline. Ann. Clin. Transl. Neurol.,  2020, 7(1), 26-35.
 [http://dx.doi.org/10.1002/acn3.50962] [PMID:  31820587]

[138]
Ferreira, S.A.; Romero-Ramos, M. Microglia response during Parkinson’s disease: Alpha-synuclein intervention. Front. Cell. Neurosci.,  2018, 12(8), 247.
 [http://dx.doi.org/10.3389/fncel.2018.00247] [PMID:  30127724]

[139]
Roh, J.S.; Sohn, D.H. Origin and List of DAMPS. Immune Netw.,  2018, 18(4), 1-14.
 [http://dx.doi.org/10.4110/in.2018.18.e27] [PMID:  30181915]

[140]
Davalos, D.; Grutzendler, J.; Yang, G.; Kim, J.V.; Zuo, Y.; Jung, S.; Littman, D.R.; Dustin, M.L.; Gan, W.B. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci.,  2005, 8(6), 752-758.
 [http://dx.doi.org/10.1038/nn1472] [PMID:  15895084]

[141]
Emmanouilidou, E.; Vekrellis, K. Exocytosis and Spreading of Normal and Aberrant α-. Synuclein. Brain Pathol.,  2016, 26(3), 398-403.
 [http://dx.doi.org/10.1111/bpa.12373] [PMID:  26940375]

[142]
Kim, C.; Ho, D.H.; Suk, J.E.; You, S.; Michael, S.; Kang, J.; Joong Lee, S.; Masliah, E.; Hwang, D.; Lee, H.J.; Lee, S.J. Neuron-released oligomeric α-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat. Commun.,  2013, 4(1), 1562.
 [http://dx.doi.org/10.1038/ncomms2534] [PMID:  23463005]

[143]
Song, N.; Chen, L.; Xie, J. Alpha-Synuclein Handling by Microglia: Activating, Combating, and Worsening. Neurosci. Bull.,  2021, 37(5), 751-753.
 [http://dx.doi.org/10.1007/s12264-021-00651-6] [PMID:  33743127]

[144]
Reynolds, A.D.; Glanzer, J.G.; Kadiu, I.; Ricardo-Dukelow, M.; Chaudhuri, A.; Ciborowski, P.; Cerny, R.; Gelman, B.; Thomas, M.P.; Mosley, R.L.; Gendelman, H.E. Nitrated alpha-synuclein-activated microglial profiling for Parkinson’s disease. J. Neurochem.,  2008, 104(6), 1504-1525.
 [http://dx.doi.org/10.1111/j.1471-4159.2007.05087.x] [PMID:  18036154]

[145]
Janda, E.; Boi, L.; Carta, A.R. Microglial phagocytosis and its regulation: A therapeutic target in parkinson’s disease? Front. Mol. Neurosci.,  2018, 11(4), 144.
 [http://dx.doi.org/10.3389/fnmol.2018.00144] [PMID:  29755317]

[146]
Choi, I.; Zhang, Y.; Seegobin, S.P.; Pruvost, M.; Wang, Q.; Purtell, K.; Zhang, B.; Yue, Z. Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration. Nat. Commun.,  2020, 11(1), 1386.
 [http://dx.doi.org/10.1038/s41467-020-15119-w] [PMID:  32170061]

[147]
Zucca, F.A.; Segura-Aguilar, J.; Ferrari, E.; Muñoz, P.; Paris, I.; Sulzer, D.; Sarna, T.; Casella, L.; Zecca, L. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease. Prog. Neurobiol.,  2017, 155, 96-119.
 [http://dx.doi.org/10.1016/j.pneurobio.2015.09.012] [PMID:  26455458]

[148]
Zecca, L.; Fariello, R.; Riederer, P.; Sulzer, D.; Gatti, A.; Tampellini, D. The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease. FEBS Lett.,  2002, 510(3), 216-220.
 [http://dx.doi.org/10.1016/S0014-5793(01)03269-0] [PMID:  11801257]

[149]
Banati, R.B.; Daniel, S.E.; Blunt, S.B. Glial pathology but absence of apoptotic nigral neurons in long-standing Parkinson’s disease. Mov. Disord.,  1998, 13(2), 221-227.
 [http://dx.doi.org/10.1002/mds.870130205] [PMID:  9539333]

[150]
Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s annd Alheimer’s disease brains. Neurology,  1988, 38(8), 1285-1291.
 [http://dx.doi.org/10.1212/WNL.38.8.1285] [PMID:  3399080]

[151]
Zecca, L.; Wilms, H.; Geick, S.; Claasen, J.H.; Brandenburg, L.O.; Holzknecht, C.; Panizza, M.L.; Zucca, F.A.; Deuschl, G.; Sievers, J.; Lucius, R. Human neuromelanin induces neuroinflammation and neurodegeneration in the rat substantia nigra: implications for Parkinson’s disease. Acta Neuropathol.,  2008, 116(1), 47-55.
 [http://dx.doi.org/10.1007/s00401-008-0361-7] [PMID:  18343932]

[152]
Zhang, W.; Phillips, K.; Wielgus, A.R.; Liu, J.; Albertini, A.; Zucca, F.A.; Faust, R.; Qian, S.Y.; Miller, D.S.; Chignell, C.F.; Wilson, B.; Jackson-Lewis, V.; Przedborski, S.; Joset, D.; Loike, J.; Hong, J.S.; Sulzer, D.; Zecca, L. Neuromelanin activates microglia and induces degeneration of dopaminergic neurons: implications for progression of Parkinson’s disease. Neurotox. Res.,  2011, 19(1), 63-72.
 [http://dx.doi.org/10.1007/s12640-009-9140-z] [PMID:  19957214]

[153]
Zhang, W.; Zecca, L.; Wilson, B.; Ren, H-W.; Wang, Y-J.; Wang, X-M.; Hong, J.S. Human neuromelanin: an endogenous microglial activator for dopaminergic neuron death. Front. Biosci.,  2013, 5(1), 1-11.
 [PMID:  23276965]

[154]
Ilijic, E.; Guzman, J.N.; Surmeier, D.J. The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson’s disease. Neurobiol. Dis.,  2011, 43(2), 364-371.
 [http://dx.doi.org/10.1016/j.nbd.2011.04.007] [PMID:  21515375]

[155]
Singh, A.; Verma, P.; Balaji, G.; Samantaray, S.; Mohanakumar, K.P. Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice. Neurochem. Int.,  2016, 99, 221-232.
 [http://dx.doi.org/10.1016/j.neuint.2016.07.003] [PMID:  27395789]

[156]
Guzman, J.N.; Ilijic, E.; Yang, B.; Sanchez-Padilla, J.; Wokosin, D.; Galtieri, D.; Kondapalli, J.; Schumacker, P.T.; Surmeier, D.J. Systemic isradipine treatment diminishes calcium-dependent mitochondrial oxidant stress. J. Clin. Invest.,  2018, 128(6), 2266-2280.
 [http://dx.doi.org/10.1172/JCI95898] [PMID:  29708514]

[157]
Simuni, T. Isradipine versus placebo in early Parkinson disease a randomized trial. Ann. Intern. Med.,  2020, 172(9), 591-598.
 [http://dx.doi.org/10.7326/M19-2534] [PMID:  32227247]

[158]
Altenhöfer, S.; Radermacher, K.A.; Kleikers, P.W.M.; Wingler, K.; Schmidt, H.H.H.W. Evolution of NADPH oxidase inhibitors: Selectivity and mechanisms for target engagement. Antioxid. Redox Signal.,  2015, 23(5), 406-427.
 [http://dx.doi.org/10.1089/ars.2013.5814] [PMID:  24383718]

[159]
Belarbi, K.; Cuvelier, E.; Destée, A.; Gressier, B.; Chartier-Harlin, M.C. NADPH oxidases in Parkinson’s disease: A systematic review. Mol. Neurodegener.,  2017, 12(1), 84.
 [http://dx.doi.org/10.1186/s13024-017-0225-5] [PMID:  29132391]

[160]
Morgenroth, V.H., III; Walters, J.R.; Roth, R.H. Dopaminergic neurons—Alteration in the kinetic properties of tyrosine hydroxylase after cessation of impulse flow. Biochem. Pharmacol.,  1976, 25(6), 655-661.
 [http://dx.doi.org/10.1016/0006-2952(76)90240-9] [PMID:  6035]

[161]
Roth, R.H.; Doherty, J.D.; Walters, J.R. Gamma-hydroxybutyrate: A role in the regulation of central dopaminergic neurons? Brain Res.,  1980, 189(2), 556-560.
 [http://dx.doi.org/10.1016/0006-8993(80)90368-6] [PMID:  7370791]

[162]
Walters, J.R.; Roth, R.H. Dopaminergic impulse neurons : Of the increase drug-induced in by antag- of activity flow’ product with. Pharmacol Exp Ther.,  1974, 191, 82-91.

[163]
Madden, T.E.; Johnson, S.W. Gamma-hydroxybutyrate is a GABAB receptor agonist that increases a potassium conductance in rat ventral tegmental dopamine neurons. J. Pharmacol. Exp. Ther.,  1998, 287(1), 261-265.
 [PMID:  9765346]

[164]
Erhardt, S.; Andersson, B.; Nissbrandt, H.; Engberg, G. Inhibition of firing rate and changes in the firing pattern of nigral dopamine neurons by γ-hydroxybutyric acid (GHBA) are specifically induced by activation of GABAB receptors. Naunyn Schmiedebergs Arch. Pharmacol.,  1998, 357(6), 611-619.
 [http://dx.doi.org/10.1007/PL00005215] [PMID:  9686936]

[165]
Kish, S.J.; O’Leary, G.; Mamelak, M.; McCluskey, T.; Warsh, J.J.; Shapiro, C.; Bies, R.; Yu, Y.; Pollock, B.; Tong, J.; Boileau, I. Does sodium oxybate inhibit brain dopamine release in humans? An exploratory neuroimaging study. Hum. Psychopharmacol.,  2021, 36(5), e2791.
 [http://dx.doi.org/10.1002/hup.2791] [PMID:  33899252]

[166]
Kolin, A.; Brezina, A.; Mamelak, M.; Pandula, E. Cardioprotective action of sodium gamma-hydroxybutyrate against isoproterenol induced myocardial damage. Int. J. Exp. Pathol.,  1993, 74(3), 275-281.
 [PMID:  8334077]

[167]
Sharmila, Q.S.; Stanely, M.P.P.; John, B. Diosmin Prevents Isoproterenol-Induced Heart Mitochondrial Oxidative Stress in Rats. Cardiovasc. Toxicol.,  2018, 18(2), 120-130.
 [http://dx.doi.org/10.1007/s12012-017-9422-2] [PMID:  28819818]

[168]
Surmeier, D.J. Beyond just connectivity — neuronal activity drives α-synuclein pathology. Mov. Disord.,  2021, 36(7), 1487-1488.
 [http://dx.doi.org/10.1002/mds.28618] [PMID:  34302385]

[169]
Yamada, K.; Iwatsubo, T. Extracellular α-synuclein levels are regulated by neuronal activity. Mol. Neurodegener.,  2018, 13(1), 9.
 [http://dx.doi.org/10.1186/s13024-018-0241-0] [PMID:  29467003]

[170]
Ueda, J.; Uemura, N.; Sawamura, M.; Taguchi, T.; Ikuno, M.; Kaji, S.; Taruno, Y.; Matsuzawa, S.; Yamakado, H.; Takahashi, R. Perampanel inhibits α-synuclein transmission in parkinson’s disease models. Mov. Disord.,  2021, 36(7), 1554-1564.
 [http://dx.doi.org/10.1002/mds.28558] [PMID:  33813737]

[171]
Bernasconi, R.; Mathivet, P.; Otten, U.; Bettler, B.; Bischoff, S.; Marescaux, C. Part of the pharmacological actions of gamma-hydroxybutyrate are mediated by GABAB receptors. In: Gamma-hydroxybutyrate; Tunnicliff, G.; Cash, C.D.; Taylor, F.R., Eds.; CRC
Press: Lonon New York, 2002; pp. 28-63.

[172]
Dexter, D.T.; Carter, C.J.; Wells, F.R.; Javoy-Agid, F.; Agid, Y.; Lees, A.; Jenner, P.; Marsden, C.D. Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J. Neurochem.,  1989, 52(2), 381-389.
 [http://dx.doi.org/10.1111/j.1471-4159.1989.tb09133.x] [PMID:  2911023]

[173]
Chen, F.; Li, X.; Aquadro, E.; Haigh, S.; Zhou, J.; Stepp, D.W.; Weintraub, N.L.; Barman, S.A.; Fulton, D.J.R. Inhibition of histone deacetylase reduces transcription of NADPH oxidases and ROS production and ameliorates pulmonary arterial hypertension. Free Radic. Biol. Med.,  2016, 99, 167-178.
 [http://dx.doi.org/10.1016/j.freeradbiomed.2016.08.003] [PMID:  27498117]

[174]
Kim, H.J.; Rowe, M.; Ren, M.; Hong, J.S.; Chen, P.S.; Chuang, D.M. Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: Multiple mechanisms of action. J. Pharmacol. Exp. Ther.,  2007, 321(3), 892-901.
 [http://dx.doi.org/10.1124/jpet.107.120188] [PMID:  17371805]

[175]
Leus, N.G.J.; Zwinderman, M.RH Dekker, FJ Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-κB-mediated inflammation. Curr. Opin. Chem. Biol.,  2016, 33, 160-168.
 [http://dx.doi.org/10.1016/j.cbpa.2016.06.019]

[176]
Xia, M.; Zhao, Q.; Zhang, H.; Chen, Y.; Yuan, Z.; Xu, Y. Proteomic analysis of HDAC3 selective inhibitor in the regulation of inflammatory response of primary microglia. Neural Plast.,  2017, 2017, 1-13.
 [http://dx.doi.org/10.1155/2017/6237351]

[177]
Klein, C.; Kemmel, V.; Taleb, O.; Aunis, D.; Maitre, M. Pharmacological doses of gamma-hydroxybutyrate (GHB) potentiate histone acetylation in the rat brain by histone deacetylase inhibition. Neuropharmacology,  2009, 57(2), 137-147.
 [http://dx.doi.org/10.1016/j.neuropharm.2009.04.013] [PMID:  19427877]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
For Visitors
DOI https://dx.doi.org/10.2174/1874467216666221103121135	Print ISSN 1874-4672
Publisher Name Bentham Science Publisher	Online ISSN 1874-4702
Current Molecular Pharmacology

The Treatment of Parkinson’s Disease with Sodium Oxybate

Abstract Play Pause

Related Journals

Related Books

Abstract
