Glutamate, Excitotoxicity and Releated Diseases

Abstract

Glutamate is an excitatory neurotransmitter that is abundant in many central and peripheral tissues and is essential for cell survival and body homeostasis. Although its existence has been known for many years, research still reveals that excitotoxicity plays a role in the development of new pathological conditions. For this reason, glutamate and glutamate excitotoxicity must be well understood, and glutamate-related circumstances must be clarified.

Keywords

• AMPAR
• EAAT
• Excitotoxicity
• Glutamate
• Kainate
• mGluR
• NMDAR

References

1. 1. Alberdi, E., et al. (2010). Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. Cell Calcium, 47(3), 264-272. https://doi.org/10.1016/j.ceca.2009.12.010
2. 2. Andreadou, E., et al. (2008). Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis. In vivo (Athens, Greece), 22(1), 137-141. https://www.ncbi.nlm.nih.gov/pubmed/18396796
3. 3. Bak, L. K., et al. (2006). The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. Journal of Neurochemistry, 98(3), 641-653. https://doi.org/10.1111/j.1471-4159.2006.03913.x
4. 4. Barone, P. (2010). Neurotransmission in Parkinson's disease: beyond dopamine. Eur J Neurol, 17(3), 364-376. https://doi.org/10.1111/j.1468-1331.2009.02900.x
5. 5. Beal, M. F. (1992). Mechanisms of excitotoxicity in neurologic diseases. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 6(15), 3338-3344. https://www.ncbi.nlm.nih.gov/pubmed/1464368
6. 6. Beck, J., et al. (2003). Na-K-Cl cotransporter contributes to glutamate-mediated excitotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience, 23(12), 5061-5068. https://doi.org/10.1523/jneurosci.23-12-05061.2003
7. 7. Berger, U. V., & Hediger, M. A. (2000). Distribution of the glutamate transporters GLAST and GLT-1 in rat circumventricular organs, meninges, and dorsal root ganglia. The Journal of comparative neurology, 421(3), 385-399. https://doi.org/10.1002/(sici)1096-9861(20000605)421:3<385::aid-cne7>3.0.co;2-s
8. 8. Bjørn-Yoshimoto, W. E., & Underhill, S. M. (2016). The importance of the excitatory amino acid transporter 3 (EAAT3). Neurochemistry International, 98, 4-18. https://doi.org/https://doi.org/10.1016/j.neuint.2016.05.007

9. 9. Blandini, F. (2010). An update on the potential role of excitotoxicity in the pathogenesis of Parkinson's disease. Functional neurology, 25(2), 65-71. https://www.ncbi.nlm.nih.gov/pubmed/20923603 10. https://www.functionalneurology.com/common/php/portiere.php? ID=76365fcd56feb7343fc6eace436ef022
10. 11. Blandini, F., et al. (1996). Glutamate and Parkinson's disease. Mol Neurobiol, 12(1), 73-94. https://doi.org/10.1007/BF02740748
11. 12. Bleich, S., et al. (2003). Glutamate and the glutamate receptor system: a target for drug action. International journal of geriatric psychiatry, 18(Suppl 1), S33-40. https://doi.org/10.1002/gps.933
12. 13. Bonnet, A.-M. (2000). Involvement of Non-Dopaminergic Pathways in Parkinson???s Disease. CNS Drugs, 13(5), 351-364. https://doi.org/10.2165/00023210-200013050-00005
13. 14. Bortolotto, Z. A., et al. (1999). Kainate receptors are involved in synaptic plasticity. Nature, 402(6759), 297-301. https://doi.org/10.1038/46290
14. 15. Cartmell, J., & Schoepp, D. D. (2000). Regulation of neurotransmitter release by metabotropic glutamate receptors. J Neurochem, 75(3), 889-907. https://doi.org/10.1046/j.1471-4159.2000.0750889.x
15. 16. Chang, P. K., et al. (2012). AMPA receptors as drug targets in neurological disease--advantages, caveats, and future outlook. The European journal of neuroscience, 35(12), 1908-1916. https://doi.org/10.1111/j.1460-9568.2012.08165.x
16. 17. Choi, D. W. (1985). Glutamate neurotoxicity in cortical cell culture is calcium dependent. Neuroscience letters, 58(3), 293-297. https://doi.org/10.1016/0304-3940(85)90069-2
17. 18. Choi, D. W., & Rothman, S. M. (1990). The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annual review of neuroscience, 13, 171-182. https://doi.org/10.1146/annurev.ne.13.030190.001131
18. 19. Cieri, D., et al. (2017). Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness. Biochemical and biophysical research communications, 483(4), 1020-1030. https://doi.org/10.1016/j.bbrc.2016.08.153
19. 20. Danbolt, N. C. (2001). Glutamate uptake. Prog Neurobiol, 65(1), 1-105. https://doi.org/10.1016/s0301-0082(00)00067-8
20. 21. De Pablo-Fernandez, E., et al. (2019). Prognosis and Neuropathologic Correlation of Clinical Subtypes of Parkinson Disease. JAMA neurology, 76(4), 470-479. https://doi.org/10.1001/jamaneurol.2018.4377
21. 22. Dickson, D. W. (2018). Neuropathology of Parkinson disease. Parkinsonism Relat Disord, 46 Suppl 1, S30-S33. https://doi.org/10.1016/j.parkreldis.2017.07.033
22. 23. Diering, G. H., & Huganir, R. L. (2018). The AMPA Receptor Code of Synaptic Plasticity. Neuron, 100(2), 314-329. https://doi.org/https://doi.org/10.1016/j.neuron.2018.10.018
23. 24. Duchen, M. R. (2004). Roles of mitochondria in health and disease. Diabetes, 53 Suppl 1, S96-102. https://doi.org/10.2337/diabetes.53.2007.s96
24. 25. Eulenburg, V., & Gomeza, J. (2010). Neurotransmitter transporters expressed in glial cells as regulators of synapse function. Brain Research Reviews, 63(1), 103-112. https://doi.org/https://doi.org/10.1016/j.brainresrev.2010.01.003
25. 26. Farooqui, T., & Farooqui, A. A. (2009). Aging: an important factor for the pathogenesis of neurodegenerative diseases. Mechanisms of ageing and development, 130(4), 203-215.
26. 27. Featherstone, D. E. (2010). Intercellular glutamate signaling in the nervous system and beyond. ACS chemical neuroscience, 1(1), 4-12. https://doi.org/10.1021/cn900006n
27. 28. Fernandez-Tome, P., et al. (2004). Beta-amyloid25-35 inhibits glutamate uptake in cultured neurons and astrocytes: modulation of uptake as a survival mechanism. Neurobiol Dis, 15(3), 580-589. https://doi.org/10.1016/j.nbd.2003.12.006
28. 29. Furness, D. N., & Lehre, K. P. (1997). Immunocytochemical localization of a high-affinity glutamate-aspartate transporter, GLAST, in the rat and guinea-pig cochlea. The European journal of neuroscience, 9(9), 1961-1969. https://doi.org/10.1111/j.1460-9568.1997.tb00763.x
29. 30. Ganor, Y., & Levite, M. (2014). The neurotransmitter glutamate and human T cells: glutamate receptors and glutamate-induced direct and potent effects on normal human T cells, cancerous human leukemia and lymphoma T cells, and autoimmune human T cells. J Neural Transm (Vienna), 121(8), 983-1006. https://doi.org/10.1007/s00702-014-1167-5
30. 31. Garcia-Esparcia, P., et al. (2018). Glutamate Transporter GLT1 Expression in Alzheimer Disease and Dementia With Lewy Bodies. Frontiers in Aging Neuroscience, 10. https://doi.org/10.3389/fnagi.2018.00122
31. 32. Gasbarri, A., & Pompili, A. (2014). 4 - Involvement of Glutamate in Learning and Memory. In A. Meneses (Ed.), Identification of Neural Markers Accompanying Memory (pp. 63-77). Elsevier. https://doi.org/https://doi.org/10.1016/B978-0-12-408139-0.00004-3
32. 33. Gill, S. S., & Pulido, O. M. (2001). Glutamate receptors in peripheral tissues: current knowledge, future research, and implications for toxicology. Toxicol Pathol, 29(2), 208-223. https://doi.org/10.1080/019262301317052486
33. 34. Han, D., et al. (2001). Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space. The Biochemical journal, 353(Pt 2), 411-416. https://doi.org/10.1042/0264-6021:3530411
34. 35. Hardingham, G. E. (2006). Pro-survival signalling from the NMDA receptor. Biochem Soc Trans, 34(Pt 5), 936-938. https://doi.org/10.1042/BST0340936
35. 36. Hardingham, G. E., & Bading, H. (2010). Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nature reviews. Neuroscience, 11(10), 682-696. https://doi.org/10.1038/nrn2911
36. 37. Hardingham, G. E., & Bading, H. (2010). Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nature reviews. Neuroscience, 11(10), 682-696. https://doi.org/10.1038/nrn2911
37. 38. Hediger, M. A. (1999). Glutamate transporters in kidney and brain. American Journal of Physiology-Renal Physiology, 277(4), F487-F492. https://doi.org/10.1152/ajprenal.1999.277.4.F487
38. 39. Henley, J. M., & Wilkinson, K. A. (2016). Synaptic AMPA receptor composition in development, plasticity and disease. Nature reviews. Neuroscience, 17(6), 337-350. https://doi.org/10.1038/nrn.2016.37
39. 40. Hetman, M., & Kharebava, G. (2006). Survival signaling pathways activated by NMDA receptors. Current topics in medicinal chemistry, 6(8), 787-799. https://doi.org/10.2174/156802606777057553
40. 41. Heuss, C., et al. (1999). G-protein-independent signaling mediated by metabotropic glutamate receptors. Nat Neurosci, 2(12), 1070-1077. https://doi.org/10.1038/15996
41. 42. Hinoi, E., et al. (2004). Glutamate signaling in peripheral tissues. Eur J Biochem, 271(1), 1-13. https://doi.org/10.1046/j.1432-1033.2003.03907.x
42. 43. Hsieh, H., et al. (2006). AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron, 52(5), 831-843. https://doi.org/10.1016/j.neuron.2006.10.035
43. 44. Huettner, J. E. (2003). Kainate receptors and synaptic transmission. Prog Neurobiol, 70(5), 387-407. https://doi.org/10.1016/s0301-0082(03)00122-9
44. 45. Johnson, J. W., & Ascher, P. (1987). Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature, 325(6104), 529-531. https://doi.org/10.1038/325529a0
45. 46. Kamat, P. K., et al. (2016). Mechanism of Oxidative Stress and Synapse Dysfunction in the Pathogenesis of Alzheimer's Disease: Understanding the Therapeutics Strategies. Mol Neurobiol, 53(1), 648-661. https://doi.org/10.1007/s12035-014-9053-6
46. 47. Kanai, Y., et al. (2013). The SLC1 high-affinity glutamate and neutral amino acid transporter family. Molecular aspects of medicine, 34(2-3), 108-120. https://doi.org/10.1016/j.mam.2013.01.001
47. 48. Katsuta, K., et al. (1995). The neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427 in focal cerebral ischemia in rats. J Cereb Blood Flow Metab, 15(2), 345-348. https://doi.org/10.1038/jcbfm.1995.40
48. 49. Komuro, H., & Rakic, P. (1993). Modulation of neuronal migration by NMDA receptors. Science, 260(5104), 95-97. https://doi.org/10.1126/science.8096653
49. 50. Koutsilieri, E., & Riederer, P. (2007). Excitotoxicity and new antiglutamatergic strategies in Parkinson's disease and Alzheimer's disease. Parkinsonism Relat Disord, 13 Suppl 3, S329-331. https://doi.org/10.1016/S1353-8020(08)70025-7
50. 51. Krebs, H. A. (1935). Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. The Biochemical journal, 29(8), 1951-1969. https://doi.org/10.1042/bj0291951
51. 52. Kuchibhotla, K. V., et al. (2008). Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron, 59(2), 214-225. https://doi.org/10.1016/j.neuron.2008.06.008
52. 53. Lau, A., & Tymianski, M. (2010). Glutamate receptors, neurotoxicity and neurodegeneration. Pflugers Arch, 460(2), 525-542. https://doi.org/10.1007/s00424-010-0809-1
53. 54. Lehre, K. P., & Danbolt, N. C. (1998). The Number of Glutamate Transporter Subtype Molecules at Glutamatergic Synapses: Chemical and Stereological Quantification in Young Adult Rat Brain. The Journal of Neuroscience, 18(21), 8751-8757. https://doi.org/10.1523/jneurosci.18-21-08751.1998
54. 55. Lehre, K. P., & Danbolt, N. C. (1998). The number of glutamate transporter subtype molecules at glutamatergic synapses: chemical and stereological quantification in young adult rat brain. The Journal of neuroscience : the official journal of the Society for Neuroscience, 18(21), 8751-8757. https://doi.org/10.1523/JNEUROSCI.18-21-08751.1998
55. 56. Lerma, J. (2006). Kainate receptor physiology. Current opinion in pharmacology, 6(1), 89-97. https://doi.org/10.1016/j.coph.2005.08.004
56. 57. Leveille, F., et al. (2008). Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 22(12), 4258-4271. https://doi.org/10.1096/fj.08-107268
57. 58. Li, F., & Tsien, J. Z. (2009). Memory and the NMDA receptors. The New England journal of medicine, 361(3), 302-303. https://doi.org/10.1056/NEJMcibr0902052
58. 59. Li, G., et al. (2015). Characterization and Regulation of the Amino Acid Transporter SNAT2 in the Small Intestine of Piglets. PLOS ONE, 10(6), e0128207. https://doi.org/10.1371/journal.pone.0128207
59. 60. Li, S., et al. (1997). Glutamate transporter alterations in Alzheimer disease are possibly associated with abnormal APP expression. J Neuropathol Exp Neurol, 56(8), 901-911. https://doi.org/10.1097/00005072-199708000-00008
60. 61. Lin, C. L., et al. (1998). Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron, 20(3), 589-602. https://doi.org/10.1016/s0896-6273(00)80997-6
61. 62. Liu, L., et al. (2004). Role of NMDA receptor subtypes in governing the direction of hippocampal synaptic plasticity. Science, 304(5673), 1021-1024. https://doi.org/10.1126/science.1096615
62. 63. Liu, Y., et al. (2007). NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience, 27(11), 2846-2857. https://doi.org/10.1523/jneurosci.0116-07.2007
63. 64. Malinow, R., & Malenka, R. C. (2002). AMPA receptor trafficking and synaptic plasticity. Annual review of neuroscience, 25, 103-126. https://doi.org/10.1146/annurev.neuro.25.112701.142758
64. 65. Maragakis, N. J., & Rothstein, J. D. (2001). Glutamate transporters in neurologic disease. Archives of neurology, 58(3), 365-370. https://doi.org/10.1001/archneur.58.3.365
65. 66. Marmiroli, P., & Cavaletti, G. (2012). The glutamatergic neurotransmission in the central nervous system. Current medicinal chemistry, 19(9), 1269-1276. https://doi.org/10.2174/092986712799462711
66. 67. Mathis, S., et al. (2017). Current view and perspectives in amyotrophic lateral sclerosis. Neural Regeneration Research, 12(2), 181. https://doi.org/10.4103/1673-5374.200794
67. 68. Mayer, M. L. (2011). Structure and mechanism of glutamate receptor ion channel assembly, activation and modulation. Current opinion in neurobiology, 21(2), 283-290. https://doi.org/10.1016/j.conb.2011.02.001
68. 69. Mayer, M. L., & Armstrong, N. (2004). Structure and function of glutamate receptor ion channels. Annu Rev Physiol, 66(1), 161-181. https://doi.org/10.1146/annurev.physiol.66.050802.084104
69. 70. Mayer, M. L., & Westbrook, G. L. (1987). The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol, 28(3), 197-276. https://doi.org/10.1016/0301-0082(87)90011-6
70. 71. Meldrum, B., & Garthwaite, J. (1990). Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci, 11(9), 379-387. https://doi.org/10.1016/0165-6147(90)90184-a
71. 72. Meldrum, B. S. (1994). The role of glutamate in epilepsy and other CNS disorders. Neurology, 44(11 Suppl 8), S14-23. https://www.ncbi.nlm.nih.gov/pubmed/7970002
72. 73. Mennerick, S., et al. (1998). Neuronal expression of the glutamate transporter GLT-1 in hippocampal microcultures. The Journal of neuroscience : the official journal of the Society for Neuroscience, 18(12), 4490-4499. https://doi.org/10.1523/JNEUROSCI.18-12-04490.1998
73. 74. Mercier, M. S., & Lodge, D. (2014). Group III metabotropic glutamate receptors: pharmacology, physiology and therapeutic potential. Neurochem Res, 39(10), 1876-1894. https://doi.org/10.1007/s11064-014-1415-y
74. 75. Muller, F. (2000). The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging. J Am Aging Assoc, 23(4), 227-253. https://doi.org/10.1007/s11357-000-0022-9
75. 76. Nicholls, D. (2004). Mitochondrial dysfunction and glutamate excitotoxicity studied in primary neuronal cultures. Current molecular medicine, 4(2), 149-177.
76. 77. Niciu, M. J., et al. (2012). Overview of glutamatergic neurotransmission in the nervous system. Pharmacology, biochemistry, and behavior, 100(4), 656-664. https://doi.org/10.1016/j.pbb.2011.08.008
77. 78. Novelli, A., et al. (1988). Glutamate Becomes Neurotoxic Via the N-Methyl-D-Aspartate Receptor When Intracellular Energy-Levels Are Reduced. Brain Research, 451(1-2), 205-212. https://doi.org/Doi 10.1016/0006-8993(88)90765-2
78. 79. O'Shea, R. D. (2002). Roles and regulation of glutamate transporters in the central nervous system. Clinical and experimental pharmacology & physiology, 29(11), 1018-1023. https://doi.org/10.1046/j.1440-1681.2002.03770.x
79. 80. Ohishi, H., et al. (1994). Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex. Neuron, 13(1), 55-66. https://doi.org/10.1016/0896-6273(94)90459-6
80. 81. Orrenius, S. (2004). Mitochondrial regulation of apoptotic cell death. Toxicology letters, 149(1-3), 19-23. https://doi.org/10.1016/j.toxlet.2003.12.017
81. 82. Ottersen, O. P. (1989). Quantitative electron microscopic immunocytochemistry of neuroactive amino acids. Anat Embryol (Berl), 180(1), 1-15. https://doi.org/10.1007/bf00321895
82. 83. Ottersen, O. P., et al. (1992). Metabolic compartmentation of glutamate and glutamine: morphological evidence obtained by quantitative immunocytochemistry in rat cerebellum. Neuroscience, 46(3), 519-534. https://doi.org/10.1016/0306-4522(92)90141-n
83. 84. Owe, S. G., et al. (2006). The ionic stoichiometry of the GLAST glutamate transporter in salamander retinal glia. The Journal of physiology, 577(Pt 2), 591-599. https://doi.org/10.1113/jphysiol.2006.116830
84. 85. Pajarillo, E., et al. (2019). The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics. Neuropharmacology, 161, 107559. https://doi.org/10.1016/j.neuropharm.2019.03.002
85. 86. Pallo, S. P., et al. (2016). Mechanisms of tau and Abeta-induced excitotoxicity. Brain Res, 1634, 119-131. https://doi.org/10.1016/j.brainres.2015.12.048
86. 87. Palmer, C. L., et al. (2005). The molecular pharmacology and cell biology of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Pharmacological reviews, 57(2), 253-277. https://doi.org/10.1124/pr.57.2.7
87. 88. Park, C. K., et al. (1988). The glutamate antagonist MK-801 reduces focal ischemic brain damage in the rat. Annals of neurology, 24(4), 543-551. https://doi.org/10.1002/ana.410240411
88. 89. Parsons, Matthew P., & Raymond, Lynn A. (2014). Extrasynaptic NMDA Receptor Involvement in Central Nervous System Disorders. Neuron, 82(2), 279-293. https://doi.org/https://doi.org/10.1016/j.neuron.2014.03.030
89. 90. Peng, T. I., & Jou, M. J. (2010). Oxidative stress caused by mitochondrial calcium overload. Ann N Y Acad Sci, 1201(1), 183-188. https://doi.org/10.1111/j.1749-6632.2010.05634.x
90. 91. Perkins, E. M., et al. (2018). Loss of cerebellar glutamate transporters EAAT4 and GLAST differentially affects the spontaneous firing pattern and survival of Purkinje cells. Human Molecular Genetics, 27(15), 2614-2627. https://doi.org/10.1093/hmg/ddy169
91. 92. Perry, T. L., et al. (1971). Free amino acids and related compounds in biopsies of human brain. J Neurochem, 18(3), 521-528. https://doi.org/10.1111/j.1471-4159.1971.tb11980.x
92. 93. Plaitakis, A., & Constantakakis, E. (1993). Altered metabolism of excitatory amino acids, N-acetyl-aspartate and N-acetyl-aspartylglutamate in amyotrophic lateral sclerosis. Brain Research Bulletin, 30(3-4), 381-386. https://doi.org/10.1016/0361-9230(93)90269-h
93. 94. Poewe, W., et al. (2017). Parkinson disease. Nature reviews. Disease primers, 3, 17013. https://doi.org/10.1038/nrdp.2017.13
94. 95. Pow, D. V., & Barnett, N. L. (2000). Developmental expression of excitatory amino acid transporter 5: a photoreceptor and bipolar cell glutamate transporter in rat retina. Neuroscience letters, 280(1), 21-24. https://doi.org/https://doi.org/10.1016/S0304-3940(99)00988-X
95. 96. Quintanilla, R. A., et al. (2012). Truncated tau and Abeta cooperatively impair mitochondria in primary neurons. Neurobiol Aging, 33(3), 619 e625-635. https://doi.org/10.1016/j.neurobiolaging.2011.02.007
96. 97. Radi, R., et al. (1991a). Peroxynitrite Oxidation of Sulfhydryls - the Cytotoxic Potential of Superoxide and Nitric-Oxide. Journal of Biological Chemistry, 266(7), 4244-4250. ://WOS:A1991FA69400037
97. 98. Radi, R., et al. (1991b). Peroxynitrite-Induced Membrane Lipid-Peroxidation - the Cytotoxic Potential of Superoxide and Nitric-Oxide. Archives of biochemistry and biophysics, 288(2), 481-487. https://doi.org/Doi 10.1016/0003-9861(91)90224-7
98. 99. Rao, V. K., et al. (2014). Mitochondrial permeability transition pore is a potential drug target for neurodegeneration. Biochimica et biophysica acta, 1842(8), 1267-1272. https://doi.org/10.1016/j.bbadis.2013.09.003
99. 100. Rauen, T., et al. (1996). Differential expression of three glutamate transporter subtypes in the rat retina. Cell and tissue research, 286(3), 325-336. https://doi.org/10.1007/s004410050702
100. 101. Rhein, V., et al. (2009). Amyloid-beta and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer's disease mice. Proceedings of the National Academy of Sciences of the United States of America, 106(47), 20057-20062. https://doi.org/10.1073/pnas.0905529106
101. 102. Riedel, G., et al. (2003). Glutamate receptor function in learning and memory. Behavioural brain research, 140(1-2), 1-47. https://doi.org/10.1016/s0166-4328(02)00272-3
102. 103. Robberecht, W., & Philips, T. (2013). The changing scene of amyotrophic lateral sclerosis. Nature reviews. Neuroscience, 14(4), 248-264. https://doi.org/10.1038/nrn3430
103. 104. Rothstein, J. D., et al. (1994). Localization of neuronal and glial glutamate transporters. Neuron, 13(3), 713-725. https://doi.org/10.1016/0896-6273(94)90038-8
104. 105. Salgo, M. G., et al. (1995). Peroxynitrite Causes DNA Nicks in Plasmid Pbr322. Biochemical and biophysical research communications, 210(3), 1025-1030. https://doi.org/DOI 10.1006/bbrc.1995.1759
105. 106. Saroff, D., et al. (2000). Selective vulnerability of spinal cord motor neurons to non-NMDA toxicity. Neuroreport, 11(5), 1117-1121. https://doi.org/10.1097/00001756-200004070-00041
106. 107. Sasaki, Y. F., et al. (2002). Characterization and comparison of the NR3A subunit of the NMDA receptor in recombinant systems and primary cortical neurons. Journal of neurophysiology, 87(4), 2052-2063.
107. 108. Sattler, R., et al. (1999). Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science, 284(5421), 1845-1848. https://doi.org/DOI 10.1126/science.284.5421.1845
108. 109. Sattler, R., et al. (2000). Distinct roles of synaptic and extrasynaptic NMDA receptors in excitotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience, 20(1), 22-33. https://doi.org/10.1523/JNEUROSCI.20-01-00022.2000
109. 110. Scott, H. A., et al. (2011). Glutamate transporter variants reduce glutamate uptake in Alzheimer's disease. Neurobiol Aging, 32(3), 553 e551-511. https://doi.org/10.1016/j.neurobiolaging.2010.03.008
110. 111. Sheng, M., et al. (2012). Synapses and Alzheimer's disease. Cold Spring Harb Perspect Biol, 4(5), a005777-a005777. https://doi.org/10.1101/cshperspect.a005777
111. 112. Small, S. A., & Duff, K. (2008). Linking Abeta and tau in late-onset Alzheimer's disease: a dual pathway hypothesis. Neuron, 60(4), 534-542. https://doi.org/10.1016/j.neuron.2008.11.007
112. 113. Song, I., & Huganir, R. L. (2002). Regulation of AMPA receptors during synaptic plasticity. Trends in Neurosciences, 25(11), 578-588. https://doi.org/https://doi.org/10.1016/S0166-2236(02)02270-1
113. 114. Surmeier, D. J., & Schumacker, P. T. (2013). Calcium, bioenergetics, and neuronal vulnerability in Parkinson's disease. The Journal of biological chemistry, 288(15), 10736-10741. https://doi.org/10.1074/jbc.R112.410530
114. 115. Surmeier, D. J., et al. (2017). Calcium and Parkinson's disease. Biochemical and biophysical research communications, 483(4), 1013-1019. https://doi.org/10.1016/j.bbrc.2016.08.168
115. 116. Talantova, M., et al. (2013). Abeta induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss. Proceedings of the National Academy of Sciences of the United States of America, 110(27), E2518-2527. https://doi.org/10.1073/pnas.1306832110
116. 117. Terasaki, Y., et al. (2010). Activation of NR2A receptors induces ischemic tolerance through CREB signaling. J Cereb Blood Flow Metab, 30(8), 1441-1449. https://doi.org/10.1038/jcbfm.2010.18
117. 118. Texido, L., et al. (2011). Amyloid beta peptide oligomers directly activate NMDA receptors. Cell Calcium, 49(3), 184-190. https://doi.org/10.1016/j.ceca.2011.02.001
118. 119. Thayer, S. A., & Wang, G. J. (1995). Glutamate-induced calcium loads: effects on energy metabolism and neuronal viability. Clinical and experimental pharmacology & physiology, 22(4), 303-304. https://doi.org/10.1111/j.1440-1681.1995.tb02004.x
119. 120. Trotti, D., et al. (1999). SOD1 mutants linked to amyotrophic lateral sclerosis selectively inactivate a glial glutamate transporter. Nature neuroscience, 2(5), 427-433. https://doi.org/10.1038/8091
120. 121. Tse, D. Y., et al. (2014). Possible roles of glutamate transporter EAAT5 in mouse cone depolarizing bipolar cell light responses. Vision Research, 103, 63-74. https://doi.org/https://doi.org/10.1016/j.visres.2014.06.005
121. 122. Vandenberg, R. J., & Ryan, R. M. (2013). Mechanisms of glutamate transport. Physiological reviews, 93(4), 1621-1657. https://doi.org/10.1152/physrev.00007.2013
122. 123. Vandenberghe, W., et al. (2000). AMPA receptor calcium permeability, GluR2 expression, and selective motoneuron vulnerability. The Journal of neuroscience : the official journal of the Society for Neuroscience, 20(1), 123-132. https://doi.org/10.1523/JNEUROSCI.20-01-00123.2000
123. 124. Wang, G. J., & Thayer, S. A. (1996). Sequestration of glutamate-induced Ca2+ loads by mitochondria in cultured rat hippocampal neurons. Journal of neurophysiology, 76(3), 1611-1621. https://doi.org/10.1152/jn.1996.76.3.1611
124. 125. Wang, K. K. W. (2000). Calpain and caspase: can you tell the difference? Trends in Neurosciences, 23(1), 20-26. https://doi.org/10.1016/s0166-2236(99)01479-4
125. 126. Wang, R., & Reddy, P. H. (2017). Role of Glutamate and NMDA Receptors in Alzheimer's Disease. J Alzheimers Dis, 57(4), 1041-1048. https://doi.org/10.3233/JAD-160763
126. 127. Weiss, J. H. (2011). Ca permeable AMPA channels in diseases of the nervous system. Front Mol Neurosci, 4, 42. https://doi.org/10.3389/fnmol.2011.00042
127. 128. Yadav, R., et al. (2017). AMPA Receptors: Molecular Biology and Pharmacology☆. In Reference Module in Neuroscience and Biobehavioral Psychology. Elsevier. https://doi.org/https://doi.org/10.1016/B978-0-12-809324-5.02325-7
128. 129. Yang, J. L., et al. (2011). The excitatory neurotransmitter glutamate stimulates DNA repair to increase neuronal resiliency. Mech Ageing Dev, 132(8-9), 405-411. https://doi.org/10.1016/j.mad.2011.06.005
129. 130. Zerangue, N., & Kavanaugh, M. P. (1996). Flux coupling in a neuronal glutamate transporter. Nature, 383(6601), 634-637. https://doi.org/10.1038/383634a0
130. 131. Zhang, Z., et al. (2019). Roles of Glutamate Receptors in Parkinson's Disease. Int J Mol Sci, 20(18), 4391. https://doi.org/10.3390/ijms20184391
131. 132. Zhu, S., & Paoletti, P. (2015). Allosteric modulators of NMDA receptors: multiple sites and mechanisms. Current opinion in pharmacology, 20, 14-23. https://doi.org/10.1016/j.coph.2014.10.009
132. 133. Zou, J., et al. (2017). Molecular Basis for Modulation of Metabotropic Glutamate Receptors and Their Drug Actions by Extracellular Ca2+. International Journal of Molecular Sciences, 18(3), 672. https://doi.org/10.3390/ijms18030672
133. 134. Zumkehr, J., et al. (2015). Ceftriaxone ameliorates tau pathology and cognitive decline via restoration of glial glutamate transporter in a mouse model of Alzheimer's disease. Neurobiol Aging, 36(7), 2260-2271.