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Central Nervous System Agents in Medicinal Chemistry

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ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

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Review Article

GABA-transaminase: A Key Player and Potential Therapeutic Target for Neurological Disorders

Author(s): Sania Grover, Raj Kumar Narang and Shamsher Singh*

Volume 24, Issue 1, 2024

Published on: 12 January, 2024

Page: [57 - 67] Pages: 11

DOI: 10.2174/0118715249267700231116053516

Price: $65

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Abstract

Neurological disorders such as epilepsy, autism, Huntington's disease, multiple sclerosis, and Alzheimer's disease alter brain functions like cognition, mood, movements, and language, severely compromising the well-being of persons, suffering from their negative effects. The neurotransmitters (GABA, glutamate, norepinephrine, dopamine) are found to be involved in neuronal signaling and neurotransmission. GABA, a "commanding neurotransmitter" is directly or indirectly associated with various neurological disorders. GABA is metabolized to succinic semialdehyde by a mitochondrial gamma-aminobutyric acid-transaminase (GABA-T) enzyme. Therefore, the alterations in the GABA performance in the distinct regions of the brain via GABA-T overstimulation or inhibition would play a vital role in the pathogenesis of various neurological disorders. This review emphasizes the leading participation of GABA-T in neurological disorders like Huntington's disease, epilepsy, autism, Alzheimer's disease, and multiple sclerosis. In Huntington's disease, epilepsy, and multiple sclerosis, the surfeited performance of GABA-T results in diminished levels of GABA, whereas in autism, the subsidence of GABA-T activity causes the elevation in GABA contents, which is responsible for behavioral changes in these disorders. Therefore, GABA-T inhibitors (in Huntington's disease, epilepsy, and multiple sclerosis) or agonists (in autism) can be used therapeutically. In the context of Alzheimer's disease, some researchers favor the stimulation of GABA-T activity whereas some disagree with it. Therefore, the activity of GABA-T concerning Alzheimer's disease is still unclear. In this way, studies of GABA-T enzymatic activity in contrast to neurological disorders could be undertaken to understand and be considered a therapeutic target for several GABA-ergic CNS diseases.

Keywords: GABA, GABA-T, epilepsy, autism, huntington's disease, multiple sclerosis, alzheimer's disease.

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[1]
Li, H.; Cao, Y. Lactic acid bacterial cell factories for gamma-aminobutyric acid. Amino Acids, 2010, 39(5), 1107-1116.
[http://dx.doi.org/10.1007/s00726-010-0582-7] [PMID: 20364279]
[2]
Sarasa, S.B.; Mahendran, R.; Muthusamy, G.; Thankappan, B.; Selta, D.R.F.; Angayarkanni, J. A brief review on the non-protein amino acid, gamma-amino butyric acid (GABA): its production and role in microbes. Curr. Microbiol., 2020, 77(4), 534-544.
[http://dx.doi.org/10.1007/s00284-019-01839-w] [PMID: 31844936]
[3]
National Center for Biotechnology Information. PubChem Compound Summary for CID 119, Gamma-Aminobutyric Acid. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Gamma-Aminobutyric-Acid (Accessed on: 24 August, 2023).
[4]
Boonstra, E.; de Kleijn, R.; Colzato, L.S.; Alkemade, A.; Forstmann, B.U.; Nieuwenhuis, S. Neurotransmitters as food supplements: The effects of GABA on brain and behavior. Front. Psychol., 2015, 6, 1520.
[http://dx.doi.org/10.3389/fpsyg.2015.01520] [PMID: 26500584]
[5]
Jewett, B.E.; Sharma, S. Physiology, GABA. In: StatPearls; StatPearls Publishing: Treasure Island, FL, 2018.
[6]
Kuffler, S.W. Mechanisms of activation and motor control of stretch receptors in lobster and crayfish. J. Neurophysiol., 1954, 17(6), 558-574.
[http://dx.doi.org/10.1152/jn.1954.17.6.558] [PMID: 13212426]
[7]
Florey, E. An inhibitory and an excitatory factor of mammalian central nervous system, and their action of a single sensory neuron. Arch. Int. Physiol., 1954, 62(1), 33-53.
[http://dx.doi.org/10.3109/13813455409145367] [PMID: 13149232]
[8]
Roberts, E.; Frankel, S. γ-aminobutyric acid in brain: Its formation from glutamic acid. J. Biol. Chem., 1950, 187(1), 55-63.
[http://dx.doi.org/10.1016/S0021-9258(19)50929-2] [PMID: 14794689]
[9]
Sherif, F.M.; Saleem Ahmed, S. Basic aspects of GABA-transaminase in neuropsychiatric disorders. Clin. Biochem., 1995, 28(2), 145-154.
[http://dx.doi.org/10.1016/0009-9120(94)00074-6] [PMID: 7628073]
[10]
Sherif, F.M. GABA-Transaminase in brain and blood platelets: Basic and clinical aspects. Prog. Neuropsychopharmacol. Biol. Psychiatry, 1994, 18(8), 1219-1233.
[http://dx.doi.org/10.1016/0278-5846(94)90089-2] [PMID: 7863013]
[11]
Seo, H.S.; Jeong, E.K.; Choi, S.; Kwon, Y.; Park, H.J.; Kim, I. Changes of neurotransmitters in youth with internet and smartphone addiction: A comparison with healthy controls and changes after cognitive behavioral therapy. AJNR Am. J. Neuroradiol., 2020, 41(7), 1293-1301.
[http://dx.doi.org/10.3174/ajnr.A6632] [PMID: 32616578]
[12]
Solas, M.; Puerta, E.; Ramirez, M. Treatment options in alzheimer s disease: The GABA story. Curr. Pharm. Des., 2015, 21(34), 4960-4971.
[http://dx.doi.org/10.2174/1381612821666150914121149] [PMID: 26365140]
[13]
Bown, A.W.; Shelp, B.J. The Metabolism and Functions of [gamma]-Aminobutyric Acid. Plant Physiol., 1997, 115(1), 1-5.
[http://dx.doi.org/10.1104/pp.115.1.1] [PMID: 12223787]
[14]
Pearl, P.L.; Gibson, K.M. Clinical aspects of the disorders of GABA metabolism in children. Curr. Opin. Neurol., 2004, 17(2), 107-113.
[http://dx.doi.org/10.1097/00019052-200404000-00005] [PMID: 15021235]
[15]
Kilb, W.; Kirischuk, S. GABA release from astrocytes in health and disease. Int. J. Mol. Sci., 2022, 23(24), 15859.
[http://dx.doi.org/10.3390/ijms232415859] [PMID: 36555501]
[16]
Lee, X.Y.; Tan, J.S.; Cheng, L.H. Gamma aminobutyric acid (GABA) enrichment in plant-based food–A mini review. Food Rev. Int., 2022, 1-22.
[http://dx.doi.org/10.1080/87559129.2022.2097257]
[17]
Neff, R.; Kambara, K.; Bertrand, D. Ligand gated receptor interactions: A key to the power of neuronal networks. Biochem. Pharmacol., 2021, 190, 114653.
[http://dx.doi.org/10.1016/j.bcp.2021.114653] [PMID: 34129858]
[18]
Tang, B.L. Amyloid precursor protein (APP) and GABAergic neurotransmission. Cells, 2019, 8(6), 550.
[http://dx.doi.org/10.3390/cells8060550] [PMID: 31174368]
[19]
Jayakumar, A.R.; Sujatha, R.; Paul, V.; Asokan, C.; Govindasamy, S.; Jayakumar, R. Role of nitric oxide on GABA, glutamic acid, activities of GABA-T and GAD in rat brain cerebral cortex. Brain Res., 1999, 837(1-2), 229-235.
[http://dx.doi.org/10.1016/S0006-8993(99)01692-3] [PMID: 10434007]
[20]
Blancquaert, L.; Baba, S.P.; Kwiatkowski, S.; Stautemas, J.; Stegen, S.; Barbaresi, S.; Chung, W.; Boakye, A.A.; Hoetker, J.D.; Bhatnagar, A.; Delanghe, J.; Vanheel, B.; Veiga-da-Cunha, M.; Derave, W.; Everaert, I. Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β-alanine transamination. J. Physiol., 2016, 594(17), 4849-4863.
[http://dx.doi.org/10.1113/JP272050] [PMID: 27062388]
[21]
Zuhra, K.; Augsburger, F.; Majtan, T.; Szabo, C. Cystathionine-β-synthase: Molecular regulation and pharmacological inhibition. Biomolecules, 2020, 10(5), 697.
[http://dx.doi.org/10.3390/biom10050697] [PMID: 32365821]
[22]
Morales, J.F.; Chuguransky, S.; Alberca, L.N.; Alice, J.I.; Goicoechea, S.; Ruiz, M.E.; Bellera, C.L.; Talevi, A. Positive predictive value surfaces as a complementary tool to assess the performance of virtual screening methods. Mini Rev. Med. Chem., 2020, 20(14), 1447-1460.
[http://dx.doi.org/10.2174/1871525718666200219130229] [PMID: 32072906]
[23]
Vega Rasgado, L.A.; Reyes, G.C.; Vega Díaz, F. Role of nitric oxide synthase on brain GABA transaminase activity and GABA levels. Acta Pharm., 2018, 68(3), 349-359.
[http://dx.doi.org/10.2478/acph-2018-0022] [PMID: 31259693]
[24]
Park, J.Y.; Lee, Y.; Lee, H.J.; Kwon, Y.S.; Chun, W. In silico screening of GABA aminotransferase inhibitors from the constituents of Valeriana officinalis by molecular docking and molecular dynamics simulation study. J. Mol. Model., 2020, 26(9), 228.
[http://dx.doi.org/10.1007/s00894-020-04495-1] [PMID: 32780180]
[25]
Wood, J.D.; Peesker, S.J.; Gorecki, D.K.J.; Tsui, D. Effect of L -cycloserine on brain GABA metabolism. Can. J. Physiol. Pharmacol., 1978, 56(1), 62-68.
[http://dx.doi.org/10.1139/y78-009] [PMID: 638858]
[26]
McManus, D.J.; Baker, G.B.; Martin, I.L.; Greenshaw, A.J.; McKenna, K.F. Effects of the antidepressant/antipanic drug phenelzine on GABA concentrations and GABA-transaminase activity in rat brain. Biochem. Pharmacol., 1992, 43(11), 2486-2489.
[http://dx.doi.org/10.1016/0006-2952(92)90331-C] [PMID: 1610412]
[27]
Valdizán, E.M.; Armijo, J.A. Effects of single and multiple increasing doses of vigabatrin on brain gaba metabolism and correlation with vigabatrin plasma concentration. Biochem. Pharmacol., 1992, 43(10), 2143-2150.
[http://dx.doi.org/10.1016/0006-2952(92)90173-G] [PMID: 1599502]
[28]
Hsu, Y.T.; Chang, Y.G.; Chern, Y. Insights into GABA A ergic system alteration in Huntington’s disease. Open Biol., 2018, 8(12), 180165.
[http://dx.doi.org/10.1098/rsob.180165] [PMID: 30518638]
[29]
Qureshi, F.H.; Qureshi, S.H.; Zia, T.; Khawaja, F. Huntington’s disease (HD): A brief review. European Journal of Public Health Studies, 2022, 5(1)
[http://dx.doi.org/10.46827/ejphs.v5i1.115]
[30]
Irfan, Z.; Khanam, S.; Karmakar, V.; Firdous, S.M.; El Khier, B.S.I.A.; Khan, I.; Rehman, M.U.; Khan, A. Pathogenesis of Huntington’s Disease: An emphasis on molecular pathways and prevention by natural remedies. Brain Sci., 2022, 12(10), 1389.
[http://dx.doi.org/10.3390/brainsci12101389] [PMID: 36291322]
[31]
Santarelli, S.; Londero, C.; Soldano, A.; Candelaresi, C.; Todeschini, L.; Vernizzi, L.; Bellosta, P. Drosophila melanogaster as a model to study autophagy in neurodegenerative diseases induced by proteinopathies. Front. Neurosci., 2023, 17, 1082047.
[http://dx.doi.org/10.3389/fnins.2023.1082047] [PMID: 37274187]
[32]
Deepa, S.; Rymbai, E.; Praveen, T.K.; Saravanan, J. Neuroprotective effects of farnesol on motor and cognitive impairment against 3-nitropropionic acid-induced Huntington’s disease. Thaiphesatchasan, 2021, 45(1), 16-23.
[33]
Schwarcz, R.; Bennett, J.P., Jr; Coyle, J.T. Inhibitors of GABA metabolism: Implications for Huntington’s disease. Ann. Neurol., 1977, 2(4), 299-303.
[http://dx.doi.org/10.1002/ana.410020407] [PMID: 152600]
[34]
Perry, T.L.; Wright, J.M.; Hansen, S.; MacLeod, P.M. Isoniazid therapy of Huntington disease. Neurology, 1979, 29(3), 370-375.
[http://dx.doi.org/10.1212/WNL.29.3.370] [PMID: 156313]
[35]
Hu, Y.Q.; Zhang, S.; Zhao, F.; Gao, C.; Feng, L.S.; Lv, Z.S.; Xu, Z.; Wu, X. Isoniazid derivatives and their anti-tubercular activity. Eur. J. Med. Chem., 2017, 133, 255-267.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.002] [PMID: 28390957]
[36]
Khazipov, R. GABAergic synchronization in epilepsy. Cold Spring Harb. Perspect. Med., 2016, 6(2), a022764.
[http://dx.doi.org/10.1101/cshperspect.a022764] [PMID: 26747834]
[37]
Gernert, M.; Feja, M. Bypassing the blood–brain barrier: Direct intracranial drug delivery in epilepsies. Pharmaceutics, 2020, 12(12), 1134.
[http://dx.doi.org/10.3390/pharmaceutics12121134] [PMID: 33255396]
[38]
Dutta, S.; Iyer, K.K.; Vanhatalo, S.; Breakspear, M.; Roberts, J.A. Mechanisms underlying pathological cortical bursts during metabolic depletion. Nat. Commun., 2023, 14(1), 4792.
[http://dx.doi.org/10.1038/s41467-023-40437-0] [PMID: 37553358]
[39]
Wang, F.; Xie, X.; Xing, X.; Sun, X. Excitatory synaptic transmission in ischemic stroke: A new outlet for classical neuroprotective strategies. Int. J. Mol. Sci., 2022, 23(16), 9381.
[http://dx.doi.org/10.3390/ijms23169381] [PMID: 36012647]
[40]
Treiman, D.M. GABAergic mechanisms in epilepsy. Epilepsia, 2001, 42(s3), 8-12.
[http://dx.doi.org/10.1046/j.1528-1157.2001.042suppl.3008.x] [PMID: 11520315]
[41]
Bradford, H.F. Glutamate, GABA and epilepsy. Prog. Neurobiol., 1995, 47(6), 477-511.
[http://dx.doi.org/10.1016/0301-0082(95)00030-5] [PMID: 8787032]
[42]
Moto, F.C.O.; Arsa’a, A.; Ngoupaye, G.T.; Taiwe, G.S.; Njapdounke, J.S.K.; Kandeda, A.K.; Nkantchoua, G.C.N.; Omam Omam, J.P.; Pale, S.; Kouemou, N.E.; Ayissi Mbomo, E.R.; Pahaye, D.B.; Ojong, L.; Mairara, V.; Ngo Bum, E. Anxiolytic and antiepileptic properties of the aqueous extract of Cissus quadrangularis (Vitaceae) in mice pilocarpine model of epilepsy. Front. Pharmacol., 2018, 9, 751.
[http://dx.doi.org/10.3389/fphar.2018.00751] [PMID: 30065650]
[43]
Ängehagen, M.; Ben-Menachem, E.; Rönnbäck, L.; Hansson, E. Novel mechanisms of action of three antiepileptic drugs, vigabatrin, tiagabine, and topiramate. Neurochem. Res., 2003, 28(2), 333-340.
[http://dx.doi.org/10.1023/A:1022393604014] [PMID: 12608706]
[44]
Lanctôt, K.L.; Amatniek, J.; Ancoli-Israel, S.; Arnold, S.E.; Ballard, C.; Cohen-Mansfield, J.; Ismail, Z.; Lyketsos, C.; Miller, D.S.; Musiek, E.; Osorio, R.S.; Rosenberg, P.B.; Satlin, A.; Steffens, D.; Tariot, P.; Bain, L.J.; Carrillo, M.C.; Hendrix, J.A.; Jurgens, H.; Boot, B. Neuropsychiatric signs and symptoms of Alzheimer’s disease: New treatment paradigms. Alzheimers Dement., 2017, 3(3), 440-449.
[http://dx.doi.org/10.1016/j.trci.2017.07.001] [PMID: 29067350]
[45]
Marcinkowska, M.; Śniecikowska, J.; Fajkis, N.; Paśko, P.; Franczyk, W.; Kołaczkowski, M. Management of dementia-related psychosis, agitation and aggression: A review of the pharmacology and clinical effects of potential drug candidates. CNS Drugs, 2020, 34(3), 243-268.
[http://dx.doi.org/10.1007/s40263-020-00707-7] [PMID: 32052375]
[46]
Paudel, Y.N.; Angelopoulou, E.; Jones, N.C.; O’Brien, T.J.; Kwan, P.; Piperi, C.; Othman, I.; Shaikh, M.F. Tau related pathways as a connecting link between epilepsy and Alzheimer’s disease. ACS Chem. Neurosci., 2019, 10(10), 4199-4212.
[http://dx.doi.org/10.1021/acschemneuro.9b00460] [PMID: 31532186]
[47]
Li, Y.; Sun, H.; Chen, Z.; Xu, H.; Bu, G.; Zheng, H. Implications of GABAergic neurotransmission in Alzheimer’s disease. Front. Aging Neurosci., 2016, 8, 31.
[http://dx.doi.org/10.3389/fnagi.2016.00031] [PMID: 26941642]
[48]
Imbimbo, B.P.; Lombard, J.; Pomara, N. Pathophysiology of Alzheimer’s disease. Neuroimaging Clin. N. Am., 2005, 15(4), 727-753. ix.
[http://dx.doi.org/10.1016/j.nic.2005.09.009] [PMID: 16443487]
[49]
Sharma, K.; Pradhan, S.; Duffy, L.K.; Yeasmin, S.; Bhattarai, N.; Schulte, M.K. Role of receptors in relation to plaques and tangles in Alzheimer’s disease pathology. Int. J. Mol. Sci., 2021, 22(23), 12987.
[http://dx.doi.org/10.3390/ijms222312987] [PMID: 34884789]
[50]
Pardillo-Díaz, R.; Pérez-García, P.; Castro, C.; Nunez-Abades, P.; Carrascal, L. Oxidative stress as a potential mechanism underlying membrane hyperexcitability in neurodegenerative diseases. Antioxidants, 2022, 11(8), 1511.
[http://dx.doi.org/10.3390/antiox11081511] [PMID: 36009230]
[51]
Calvo-Flores Guzmán, B.; Vinnakota, C.; Govindpani, K.; Waldvogel, H.J.; Faull, R.L.M.; Kwakowsky, A. The GABAergic system as a therapeutic target for Alzheimer’s disease. J. Neurochem., 2018, 146(6), 649-669.
[http://dx.doi.org/10.1111/jnc.14345] [PMID: 29645219]
[52]
Louzada, P.R.; Lima, A.C.P.; Mendonca-Silva, D.L.; Noël, F.; De Mello, F.G.; Ferreira, S.T. Taurine prevents the neurotoxicity of β-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer’s disease and other neurological disorders. FASEB J., 2004, 18(3), 511-518.
[http://dx.doi.org/10.1096/fj.03-0739com] [PMID: 15003996]
[53]
Manzano, S.; Agüera, L.; Aguilar, M.; Olazarán, J. A review on tramiprosate (Homotaurine) in alzheimer’s disease and other neurocognitive disorders. Front. Neurol., 2020, 11, 614.
[http://dx.doi.org/10.3389/fneur.2020.00614] [PMID: 32733362]
[54]
Caltagirone, C.; Ferrannini, L.; Marchionni, N.; Nappi, G.; Scapagnini, G.; Trabucchi, M. The potential protective effect of tramiprosate (homotaurine) against Alzheimer’s disease: A review. Aging Clin. Exp. Res., 2012, 24(6), 580-587.
[http://dx.doi.org/10.3275/8585] [PMID: 22961121]
[55]
Lee, B.Y.; Ban, J.Y.; Seong, Y.H. Chronic stimulation of GABAA receptor with muscimol reduces amyloid β protein (25–35)-induced neurotoxicity in cultured rat cortical cells. Neurosci. Res., 2005, 52(4), 347-356.
[http://dx.doi.org/10.1016/j.neures.2005.04.008] [PMID: 15896866]
[56]
Winkelman, M.J.; Szabo, A.; Frecska, E. The potential of psychedelics for the treatment of Alzheimer’s disease and related dementias. Eur. Neuropsychopharmacol., 2023, 76, 3-16.
[http://dx.doi.org/10.1016/j.euroneuro.2023.07.003] [PMID: 37451163]
[57]
Shao, H.; Zhang, Y.; Dong, Y.; Yu, B.; Xia, W.; Xie, Z. Chronic treatment with anesthetic propofol improves cognitive function and attenuates caspase activation in both aged and Alzheimer’s disease transgenic mice. J. Alzheimers Dis., 2014, 41(2), 499-513.
[http://dx.doi.org/10.3233/JAD-132792] [PMID: 24643139]
[58]
Aisen, P.S.; Gauthier, S.; Ferris, S.H.; Saumier, D.; Haine, D.; Garceau, D.; Duong, A.; Suhy, J.; Oh, J.; Lau, W.C.; Sampalis, J. Tramiprosate in mild-to-moderate Alzheimer’s disease-a randomized, double-blind, placebo-controlled, multi-centre study (the Alphase Study). Arch. Med. Sci., 2011, 1(1), 102-111.
[http://dx.doi.org/10.5114/aoms.2011.20612] [PMID: 22291741]
[59]
Zhang, Y.; Shan, G.J.; Zhang, Y.X.; Cao, S.J.; Zhu, S.N.; Li, H.J.; Ma, D.; Wang, D.X. Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults. Br. J. Anaesth., 2018, 121(3), 595-604.
[http://dx.doi.org/10.1016/j.bja.2018.05.059] [PMID: 30115258]
[60]
Zhang, Y.; Zhen, Y.; Dong, Y.; Xu, Z.; Yue, Y.; Golde, T.E.; Tanzi, R.E.; Moir, R.D.; Xie, Z. Anesthetic propofol attenuates the isoflurane-induced caspase-3 activation and Aβ oligomerization. PLoS One, 2011, 6(11), e27019.
[http://dx.doi.org/10.1371/journal.pone.0027019] [PMID: 22069482]
[61]
Zhang, Y.; Shao, H.; Dong, Y.; Swain, C.A.; Yu, B.; Xia, W.; Xie, Z. Chronic treatment with anesthetic propofol attenuates β-amyloid protein levels in brain tissues of aged mice. Transl. Neurodegener., 2014, 3(1), 8.
[http://dx.doi.org/10.1186/2047-9158-3-8] [PMID: 24725331]
[62]
Sherif, F.; Gottfries, C.G.; Alafuzoff, I.; Oreland, L. Brain gamma aminobutyrate aminotransferase (GABA-T) and monoamine oxidase (MAO) in patients with Alzheimer’s disease. J. Neural Transm. Park. Dis. Dement. Sect., 1992, 4(3), 227-240.
[http://dx.doi.org/10.1007/BF02260906] [PMID: 1627256]
[63]
Aoyagi, T.; Wada, T.; Kojima, F.; Nagai, M.; Harada, S.; Takeuchi, T.; Hirokawa, K. Increase in aminobutyrate aminotransferase and cholineacetyltransferase in cerebrum of aged rats. Chem. Pharm. Bull., 1990, 38(6), 1750-1752.
[http://dx.doi.org/10.1248/cpb.38.1750] [PMID: 2208390]
[64]
Paudel, R.; Raj, K.; Gupta, Y.K.; Singh, S. Oxiracetam and zinc ameliorates autism-like symptoms in propionic acid model of rats. Neurotox. Res., 2020, 37(4), 815-826.
[http://dx.doi.org/10.1007/s12640-020-00169-1] [PMID: 32026359]
[65]
Samsam, M.; Ahangari, R.; Naser, S.A. Pathophysiology of autism spectrum disorders: Revisiting gastrointestinal involvement and immune imbalance. World J. Gastroenterol., 2014, 20(29), 9942-9951.
[http://dx.doi.org/10.3748/wjg.v20.i29.9942] [PMID: 25110424]
[66]
McDougle, C.J.; Erickson, C.A.; Stigler, K.A.; Posey, D.J. Neurochemistry in the pathophysiology of autism. J. Clin. Psychiatry, 2005, 66(Suppl. 10), 9-18.
[PMID: 16401145]
[67]
Coghlan, S.; Horder, J.; Inkster, B.; Mendez, M.A.; Murphy, D.G.; Nutt, D.J. GABA system dysfunction in autism and related disorders: From synapse to symptoms. Neurosci. Biobehav. Rev., 2012, 36(9), 2044-2055.
[http://dx.doi.org/10.1016/j.neubiorev.2012.07.005] [PMID: 22841562]
[68]
Cohen, B.I. Use of a GABA-transaminase agonist for treatment of infantile autism. Med. Hypotheses, 2002, 59(1), 115-116.
[http://dx.doi.org/10.1016/S0306-9877(02)00157-3] [PMID: 12160695]
[69]
van Kooten, I.A.J.; Hof, P.R.; van Engeland, H.; Steinbusch, H.W.M.; Patterson, P.H.; Schmitz, C. Autism: neuropathology, alterations of the GABAergic system, and animal models. Int. Rev. Neurobiol., 2005, 71, 1-26.
[http://dx.doi.org/10.1016/S0074-7742(05)71001-1] [PMID: 16512344]
[70]
Mirza, R.; Sharma, B. A selective peroxisome proliferator-activated receptor-γ agonist benefited propionic acid induced autism-like behavioral phenotypes in rats by attenuation of neuroinflammation and oxidative stress. Chem. Biol. Interact., 2019, 311, 108758.
[http://dx.doi.org/10.1016/j.cbi.2019.108758] [PMID: 31348919]
[71]
Al-Lahham, S.H.; Peppelenbosch, M.P.; Roelofsen, H.; Vonk, R.J.; Venema, K. Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2010, 1801(11), 1175-1183.
[http://dx.doi.org/10.1016/j.bbalip.2010.07.007]
[72]
Tiwari, A.; Khera, R.; Rahi, S.; Mehan, S.; Makeen, H.A.; Khormi, Y.H.; Rehman, M.U.; Khan, A. Neuroprotective effect of α-mangostin in ameliorating propionic acid-induced experimental model of autism in Wistar rats. Brain Sci., 2021, 11(3), 288.
[http://dx.doi.org/10.3390/brainsci11030288] [PMID: 33669120]
[73]
Abdelli, L.S.; Samsam, A.; Naser, S.A. Propionic acid induces gliosis and neuro-inflammation through modulation of PTEN/AKT pathway in autism spectrum disorder. Sci. Rep., 2019, 9(1), 8824.
[http://dx.doi.org/10.1038/s41598-019-45348-z] [PMID: 31217543]
[74]
Morland, C.; Frøland, A.S.; Pettersen, M.N.; Storm-Mathisen, J.; Gundersen, V.; Rise, F.; Hassel, B. Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA accumulation and lethargy in a model of propionic acidemia. Biochem. J., 2018, 475(4), 749-758.
[http://dx.doi.org/10.1042/BCJ20170814] [PMID: 29339464]
[75]
Dhossche, D.; Applegate, H.; Abraham, A.; Maertens, P.; Bland, L.; Bencsath, A.; Martinez, J. Elevated plasma gamma-aminobutyric acid (GABA) levels in autistic youngsters: Stimulus for a GABA hypothesis of autism. Med. Sci. Monit., 2002, 8(8), PR1-PR6.
[PMID: 12165753]
[76]
Dobson, R.; Giovannoni, G. Multiple sclerosis-a review. Eur. J. Neurol., 2019, 26(1), 27-40.
[http://dx.doi.org/10.1111/ene.13819] [PMID: 30300457]
[77]
Pukoli, D.; Vécsei, L. Smouldering Lesion in MS: Microglia, lymphocytes and pathobiochemical mechanisms. Int. J. Mol. Sci., 2023, 24(16), 12631.
[http://dx.doi.org/10.3390/ijms241612631] [PMID: 37628811]
[78]
Kapoor, T.; Mehan, S. Neuroprotective methodologies in the treatment of multiple sclerosis current status of clinical and pre-clinical findings. Curr. Drug Discov. Technol., 2021, 18(1), 31-46.
[http://dx.doi.org/10.2174/1570163817666200207100903] [PMID: 32031075]
[79]
Sospedra, M.; Martin, R. Immunology of multiple sclerosis. Annu. Rev. Immunol., 2005, 23(1), 683-747.
[http://dx.doi.org/10.1146/annurev.immunol.23.021704.115707] [PMID: 15771584]
[80]
Bhandage, A.K.; Jin, Z.; Korol, S.V.; Shen, Q.; Pei, Y.; Deng, Q.; Espes, D.; Carlsson, P.O.; Kamali-Moghaddam, M.; Birnir, B. GABA regulates release of inflammatory cytokines from peripheral blood mononuclear cells and CD4+ T cells and is immunosuppressive in type 1 diabetes. EBioMedicine, 2018, 30, 283-294.
[http://dx.doi.org/10.1016/j.ebiom.2018.03.019] [PMID: 29627388]
[81]
Stamoula, E.; Siafis, S.; Dardalas, I.; Ainatzoglou, A.; Matsas, A.; Athanasiadis, T.; Sardeli, C.; Stamoulas, K.; Papazisis, G. Antidepressants on multiple sclerosis: A review of in vitro and in vivo models. Front. Immunol., 2021, 12, 677879.
[http://dx.doi.org/10.3389/fimmu.2021.677879] [PMID: 34093579]
[82]
Benson, C.A.; Wong, G.; Tenorio, G.; Baker, G.B.; Kerr, B.J. The MAO inhibitor phenelzine can improve functional outcomes in mice with established clinical signs in experimental autoimmune encephalomyelitis (EAE). Behav. Brain Res., 2013, 252, 302-311.
[http://dx.doi.org/10.1016/j.bbr.2013.06.019] [PMID: 23777648]
[83]
Ishikawa, A.; Ishiguro, S.I.; Tamai, M. Changes in GABA metabolism in streptozotocin-induced diabetic rat retinas. Curr. Eye Res., 1996, 15(1), 63-71.
[http://dx.doi.org/10.3109/02713689609017612] [PMID: 8631205]
[84]
Lingeshwar, P.; Kaur, G.; Singh, N.; Singh, S.; Mishra, A.; Shukla, S.; Ramakrishna, R.; Laxman, T.S.; Bhatta, R.S.; Siddiqui, H.H.; Hanif, K. A study on the involvement of GABA-transaminase in MCT induced pulmonary hypertension. Pulm. Pharmacol. Ther., 2016, 36, 10-21.
[http://dx.doi.org/10.1016/j.pupt.2015.11.002] [PMID: 26608704]
[85]
Ferenci, P.; Jacobs, R.; Pappas, S.C.; Schafer, D.F.; Jones, E.A. Enzymes of cerebral GABA metabolism and synaptosomal GABA uptake in acute liver failure in the rabbit: Evidence for decreased cerebral GABA-transaminase activity. J. Neurochem., 1984, 42(5), 1487-1490.
[http://dx.doi.org/10.1111/j.1471-4159.1984.tb02816.x] [PMID: 6707648]
[86]
Sawynok, J. Gabaergic mechanisms in antinociception. Prog. Neuropsychopharmacol. Biol. Psychiatry, 1984, 8(4-6), 581-586.
[http://dx.doi.org/10.1016/0278-5846(84)90018-6] [PMID: 6085175]

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