Метаботропные глутаматные рецепторы первой группы (mGluR1/5) и нейродегенеративные заболевания
- Авторы: Солнцева Е.И.1, Рогозин П.Д.1, Скребицкий В.Г.1
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Учреждения:
- ФГБНУ «Научный центр неврологии»
- Выпуск: Том 13, № 4 (2019)
- Страницы: 54-64
- Раздел: Обзоры
- Дата подачи: 26.12.2019
- Дата публикации: 26.12.2019
- URL: https://annaly-nevrologii.com/journal/pathID/article/view/620
- DOI: https://doi.org/10.25692/ACEN.2019.4.8
- ID: 620
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Полный текст
Аннотация
В обзоре описано участие метаботропных глутаматных рецепторов группы mGluR1/5 в механизмах нейродегенеративных заболеваний и опыт их использования в качестве терапевтической мишени на животных моделях. mGluR1/5 локализованы преимущественно на постсинаптической мембране нервной клетки, где они контактируют с двумя белками — Gαq/11 и Homer, посредством которых запускается несколько биохимических каскадов. Каскад белка Gαq/11 включает выброс Са2+ из эндоплазматического ретикулума (ER) через рецепторы к инозитол-1,4,5-трифосфату (IP3R) и активацию депо-управляемого входа Са2+. Каскад белка Gαq/11 включает также производство диацилглицерола с последующей активацией различных протеинкиназ и влиянием на геном. Белок Homer прямо контактирует с NMDA-рецепторами и опорными белками Shank, посредством которых он регулирует активность различных протеинкиназ, в том числе Akt и ERK1/2. Активация mGluR1/5 приводит к индукции длительной депрессии глутаматергической передачи, механизмом которой служит эндоцитоз AMPA-рецепторов, вызванный изменением уровня фосфорилирования белков и активацией генома.
Предполагается, что mGluR1/5 играют важную роль в патогенезе нейродегенеративных заболеваний. При болезни Альцгеймера mGluR1/5 выступают в качестве одной из мишеней для β-амилоидного пептида. Антагонисты mGluR1/5 вызывают нейропротекторный эффект на трансгенных мышах с болезнью Альцгеймера. Патогенез болезни Альцгеймера включает повышенный выброс Са2+ из ER благодаря патологической активности mGluR1/5, а также влиянию мутированного пресенилин-белка на Са2+ гомеостаз в ER. При этом восстановление уровня Са2+ в ER нарушено из-за влияния пресенилин-белка на депо-управляемый вход Са2+.
mGluR5 (но не mGluR1) рассматривают в качестве потенциальной терапевтической мишени для лечения болезни Паркинсона. Многочисленные работы, выполненные на моделях болезни Паркинсона на грызунах и приматах, выявили выраженный антипаркинсональный эффект при применении антагонистов mGluR5. Механизмы нейропротекторного действия антагонистов mGluR5 связывают с ограничением повышения внутриклеточного Са2+ благодаря снижению активации IP3- и NMDA-рецепторов. Болезнь Гентингтона связывают с мутацией гена HTT и способностью мутированного белка mhht сенситизировать IP3- и NMDA-рецепторы, вызывая тем самым перегрузку Са2+ в нейронах. Нейропротекторный эффект на трансгенных мышах с болезнью Гентингтона был получен при применении положительных аллостерических модуляторов mGluR5, которые способны избирательно включать каскад, связанный с белком Homer и вызывающий активацию Akt.
Об авторах
Елена Ивановна Солнцева
ФГБНУ «Научный центр неврологии»
Автор, ответственный за переписку.
Email: synaptology@mail.ru
Россия, Москва
Павел Денисович Рогозин
ФГБНУ «Научный центр неврологии»
Email: synaptology@mail.ru
Россия, Москва
Владимир Георгиевич Скребицкий
ФГБНУ «Научный центр неврологии»
Email: synaptology@mail.ru
Россия, Москва
Список литературы
- Ribeiro F.M., Vieira L.B., Pires R.G. et al. Metabotropic glutamate receptors and neurodegenerative diseases. Pharmacol Res 2017; 115: 179–191. doi: 10.1016/j.phrs.2016.11.013. PMID: 27872019.
- Conn P.J., Battaglia G., Marino M.J., Nicoletti F. Metabotropic glutamate receptors in the basal ganglia motor circuit. Nat Rev Neurosci 2005; 6: 787–798. doi: 10.1038/nrn1763. PMID: 16276355.
- Перфилова В.Н., Тюренков И.Н. Глутаматные метаботропные рецепторы: структура, локализация, функции. Успехи физиологических наук 2016; 2: 98–112.
- Masilamoni G.J., Smith Y. Metabotropic glutamate receptors: targets for neuroprotective therapies in Parkinson disease. Curr Opin Pharmacol 2018; 38: 72–80. doi: 10.1016/j.coph.2018.03.004. PMID: 29605730.
- Архипов В.И., Капралова М.В. Метаботропные глутаматные рецепторы как мишени для создания новых фармакологических средств. Экспериментальная и клиническая фармакология 2011; 10: 46–52. doi: 10.30906/0869-2092-2011-74-10-46–52.
- Secondo A., Bagetta G., Amantea D. On the role of store-operated calcium entry in acute and chronic neurodegenerative diseases. Front Mol Neurosci 2018; 11: 87. doi: 10.3389/fnmol.2018.00087. PMID: 29623030.
- Tang T.S., Slow E., Lupu V. et al. Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease. Proc Natl Acad Sci USA 2005; 102: 2602–2607. doi: 10.1073/pnas.0409402102. PMID: 15695335.
- Rong R., Ahn J.Y., Huang H. et al. PI3 kinase enhancer-Homer complex couples mGluRI toPI3 kinase, preventing neuronal apoptosis. Nat Neurosci 2003; 6: 1153–1161. doi: 10.1038/nn1134. PMID: 14528310.
- Bruno V., Battaglia G., Copani A. et al. An activity-dependent switch from facilitation to inhibition in the control of excitotoxicity by group I metabotropic glutamate receptors. Eur J Neurosci 2001; 13: 1469–1478. doi: 10.1046/j.0953-816x.2001.01541.x. PMID: 11328342.
- Wegierski T., Kuznicki J. Neuronal calcium signaling via store-operated channels in health and disease. Cell Calcium 2018; 74:102–111. doi: 10.1016/j.ceca.2018.07.001. PMID: 30015245.
- Zhang H., Wu L., Pchitskaya E. et al. Neuronal store-operated calcium entry and mushroom spine loss in amyloid precursor protein knock-in mouse model of Alzheimer's disease. J Neurosci 2015; 35: 13275–13286. doi: 10.1523/JNEUROSCI.1034-15.2015. PMID: 26424877.
- Lüscher C., Huber K.M. Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 2010; 65: 445–459. doi: 10.1016/j.neuron.2010.01.016. PMID: 20188650.
- Gladding C.M., Fitzjohn S.M., Molnár E. Metabotropic glutamate receptor-mediated long-term depression: molecular mechanisms. Pharmacol Rev 2009; 61: 395–412. doi: 10.1124/pr.109.001735. PMID: 19926678.
- Ménard C., Quirion R. Group 1 metabotropic glutamate receptor function and its regulation of learning and memory in the aging brain. Front Pharmacol 2012; 3: 182. doi: 10.3389/fphar.2012.00182. PMID: 23091460.
- Mameli M., Balland B., Luján R., Lüscher C. Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area. Science 2007; 317(5837): 530–533. doi: 10.1126/science.1142365. PMID: 17656725.
- Jones O.D. Do group I metabotropic glutamate receptors mediate LTD? Neurobiol Learn Mem 2017; 138: 85–97. doi: 10.1016/j.nlm.2016.08.010. PMID: 27545442.
- Pick J.E., Ziff E.B. Regulation of AMPA receptor trafficking and exit from the endoplasmic reticulum. Mol Cell Neurosci 2018; 91: 3–9. doi: 10.1016/j.mcn.2018.03.004. PMID: 29545119.
- Рогозин П.Д., Солнцева Е.И., Скребицкий В.Г. Агонист сигма1-рецепторов усиливает длительную депрессию, вызванную активацией метаботропных глутаматных рецепторов в нейронах гиппокампа крысы. Анналы клинической и экспериментальной неврологии 2018; 12(4): 57–61. doi: 10.25692/ACEN.2018.4.8.
- Glenner G.G., Wong C.W. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120: 885–890. doi: 10.1016/s0006-291x(84)80190-4. PMID: 6375662.
- Grundke-Iqbal I., Iqbal K., Tung Y.C. et al. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986; 3: 4913–4917. doi: 10.1073/pnas.83.13.4913. PMID: 3088567.
- Karch C.M., Goate A.M. Alzheimer's disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry 2015; 77: 43–51. doi: 10.1016/j.biopsych.2014.05.006. PMID: 24951455.
- Walsh D.M., Selkoe D.J. A beta oligomers − a decade of discovery. J Neurochem 2007; 101: 1172–1184. doi: 10.1111/j.1471-4159.2006.04426.x. PMID: 17286590.
- Lustbader J.W., Cirilli M., Lin C. et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer’s disease. Science 2004; 304: 448–452. doi: 10.1126/science.1091230. PMID: 15087549.
- Berridge M.J. Calcium regulation of neural rhythms, memory and Alzheimer’s disease. J Physiol 2014; 592: 281–293. doi: 10.1113/jphysiol.2013.257527. PMID: 23753528.
- Demuro A., Parker I., Stutzmann G.E. Calcium signaling and amyloid toxicity in Alzheimer disease. J Biol Chem 2010; 285: 12463–12468. doi: 10.1074/jbc.R109.080895. PMID: 20212036.
- 26. Blanchard B.J., Thomas V.L., Ingram V.M. Mechanism of membrane depolarization caused by the Alzheimer Abeta1-42 peptide. Biochem Biophys Res Commun 2002; 293: 1197–1203. doi: 10.1016/S0006-291X(02)00346-7. PMID: 12054502.
- Glass C.K., Saijo K., Winner B. et al. Mechanisms underlying inflammation in neurodegeneration. Cell 2010; 140: 918–934. doi: 10.1016/j.cell.2010.02.016. PMID: 20303880.
- Guglielmotto M., Giliberto L., Tamagno E., Tabaton M. Oxidative stress mediates the pathogenic effect of different Alzheimer’s disease risk factors. Front Aging Neurosci 2010; 2: 3. doi: 10.3389/neuro.24.003.2010. PMID: 20552043.
- Lacor P.N., Buniel M.C., Chang L. et al. Synaptic targeting by Alzheimer’s-related amyloid beta oligomers. J Neurosci 2004; 24: 10191–10200. doi: 10.1523/JNEUROSCI.3432-04.2004. PMID: 15537891.
- Hsieh H., Boehm J., Sato C. et al. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 2006; 52: 831–843. doi: 10.1016/j.neuron.2006.10.035. PMID: 17145504.
- Renner M., Lacor P.N., Velasco P.T. et al. Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5. Neuron 2010; 66: 739–754. DOI: 0.1016/j.neuron.2010.04.029. PMID: 20547131.
- Chen X., Lin R., Chang L. et al. Enhancement of long-term depression by soluble amyloid beta protein in rat hippocampus is mediated by metabotropic glutamate receptor and involves activation of p38MAPK, STEP and caspase-3. Neuroscience 2013; 253: 435–443. doi: 10.1016/j.neuroscience.2013.08.054. PMID: 24012839.
- Shankar G.M., Li S., Mehta T.H. et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 2008; 14: 837–842. doi: 10.1038/nm1782. PMID: 18568035.
- Hamilton A., Zamponi G.W., Ferguson S.S. Glutamate receptors function as scaffolds for the regulation of beta-amyloid and cellular prion protein signaling complexes. Mol Brain 2015; 8: 18. doi: 10.1186/s13041-015-0107-0. PMID: 25888324.
- Um J.W., Kaufman A.C., Kostylev M. et al. Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer abeta oligomer bound to cellular prion protein. Neuron 2013; 79: 887–902. doi: 10.1016/j.neuron.2013.06.036. PMID: 24012003.
- Hamilton A., Vasefi M., Vander Tuin C. et al. Chronic pharmacological mGluR5 inhibition prevents cognitive impairment and reduces pathogenesis in an alzheimer disease mouse model. Cell Rep 2016; 15: 1859–1865. doi: 10.1016/j.celrep.2016.04.077. PMID: 27210751.
- Khachaturian Z.S. Calcium, membranes, aging, and Alzheimer's disease. Introduction and overview. Ann NY Acad Sci 1989; 568: 1–4. doi: 10.1111/j.1749-6632.1989.tb12485.x. PMID: 2629579.
- Briggs C.A., Chakroborty S., Stutzmann G.E. Emerging pathways driving early synaptic pathology in Alzheimer's disease. Biochem Biophys Res Commun 2017; 483: 988–997. doi: 10.1016/j.bbrc.2016.09.088. PMID: 27659710.
- Zeiger W., Vetrivel K.S., Buggia-Prévot V. et al. Ca2+ influx through store-operated Ca2+ channels reduces Alzheimer disease β-amyloid peptide secretion. J Biol Chem 2013; 288: 26955–26966. doi: 10.1074/jbc.M113.473355. PMID: 23902769.
- Del Prete D., Checler F., Chami M. Ryanodine receptors: physiological function and deregulation in Alzheimer disease. Mol Neurodegener 2014; 9: 21. doi: 10.1186/1750-1326-9-21. PMID: 24902695.
- Duggan S.P., McCarthy J.V. Beyond γ-secretase activity: The multifunctional nature of presenilins in cell signalling pathways. Cell Signal 2016; 28: 1-11. doi: 10.1016/j.cellsig.2015.10.006. PMID: 26498858.
- Pannaccione A., Secondo A., Molinaro P. et al. A new concept: Aβ1-42 generates a hyperfunctional proteolytic NCX3 fragment that delays caspase-12 activation and neuronal death. J Neurosci 2012; 32: 10609-10617. doi: 10.1523/JNEUROSCI.6429-11.2012. PMID: 22855810.
- Nelson O., Supnet C., Tolia A. et al. Mutagenesis mapping of the presenilin 1 calcium leak conductance pore. J Biol Chem 2011; 286: 22339–22347. doi: 10.1074/jbc.M111.243063. PMID: 21531718.
- Green K.N., Demuro A., Akbari Y. et al. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta production. J Cell Biol 2008; 181: 1107–1116. doi: 10.1083/jcb.200706171. PMID: 18591429.
- Cheung K.H., Shineman D., Müller M. et al. Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating. Neuron 2008; 58: 871–883. doi: 10.1016/j.neuron.2008.04.015. PMID: 18579078.
- Shilling D., Müller M., Takano H. et al. Suppression of InsP3 receptor-mediated Ca2+ signaling alleviates mutant presenilin-linked familial Alzheimer's disease pathogenesis. J Neurosci 2014; 34: 6910–6923. doi: 10.1523/JNEUROSCI.5441-13.2014. PMID: 24828645.
- Stutzmann G.E., Smith I., Caccamo A. et al. Enhanced ryanodine-mediated calcium release in mutant PS1-expressing Alzheimer's mouse models. Ann N Y Acad Sci 2007; 1097: 265–277. doi: 10.1196/annals.1379.025. PMID: 17413028.
- Hayrapetyan V., Rybalchenko V., Rybalchenko N., Koulen P. The N-terminus of presenilin-2 increases single channel activity of brain ryanodine receptors through direct protein-protein interaction. Cell Calcium 2008; 44: 507–518. doi: 10.1016/j.ceca.2008.03.004. PMID: 18440065.
- Stutzmann G.E., Smith I., Caccamo A. et al. Enhanced ryanodine receptor recruitment contributes to Ca2+ disruptions in young, adult, and aged Alzheimer's disease mice. J Neurosci 2006; 26: 5180–5189. doi: 10.1523/JNEUROSCI.0739-06.2006. PMID: 16687509.
- Chakroborty S., Briggs C., Miller M.B. et al. Stabilizing ER Ca2+ channel function as an early preventative strategy for Alzheimer's disease. PLoS One 2012; 7: e52056. doi: 10.1371/journal.pone.0052056. PMID: 23284867.
- Oulès B., Del Prete D., Greco B. et al. Ryanodine receptor blockade reduces amyloid-β load and memory impairments in Tg2576 mouse model of Alzheimer disease. J Neurosci 2012; 32: 11820–11834. doi: 10.1523/JNEUROSCI.0875-12.2012. PMID: 22915123.
- Peng J., Liang G., Inan S. et al. Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice. Neurosci Lett 2012; 516: 274–279. doi: 10.1016/j.neulet.2012.04.008. PMID: 22516463.
- Sun S., Zhang H., Liu J. et al. Reduced synaptic STIM2 expression and impaired store-operated calcium entry cause destabilization of mature spines in mutant presenilin mice. Neuron 2014 82: 79–93. doi: 10.1016/j.neuron.2014.02.019. PMID: 24698269.
- Garcia-Alvarez G., Shetty M.S., Lu B. et al. Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes. Front Behav Neurosci 2015; 9: 180. doi: 10.3389/fnbeh.2015.00180. PMID: 26236206 .
- Zhang H., Sun S., Wu L. et al. Store-operated calcium channel complex in postsynaptic spines: a new therapeutic target for Alzheimer's disease treatment. J Neurosci 2016; 36: 11837–11850. doi: 10.1523/JNEUROSCI.1188-16.2016. PMID: 27881772.
- Frisina P.G., Haroutunian V., Libow L.S. The neuropathological basis for depression in Parkinson’s disease. Parkinsonism Relat Disord 2009; 15: 144–148. doi: 10.1016/j.parkreldis.2008.04.038. PMID: 18571456.
- Lee F.J., Liu F. Genetic factors involved in the pathogenesis of Parkinson’s disease. Brain Res Rev 2008; 58: 354–364. doi: 10.1016/j.brainresrev.2008.02.001. PMID: 18313759.
- Bartels A.L., Leenders K.L. Parkinson’s disease: the syndrome, the pathogenesis and pathophysiology. Cortex 2009; 45: 915–921. doi: 10.1016/j.cortex.2008.11.010. PMID: 19095226.
- Dauer W., Przedborski S. Parkinson’s disease: mechanisms and models. Neuron 2003; 39: 889–909. doi: 10.1016/s0896-6273(03)00568-3. PMID: 12971891.
- Hornykiewicz O. Chemical neuroanatomy of the basal ganglia–normal and in Parkinson's disease. J Chem Neuroanat 2001; 22: 3–12. doi: 10.1016/s0891-0618(01)00100-4. PMID: 11470551.
- DeLong M.R., Wichmann T. Basal ganglia circuits as targets for neuromodulation in parkinson disease. JAMA Neurol 2015; 72: 1354–1360. doi: 10.1001/jamaneurol.2015.2397. PMID: 26409114.
- Benbir G., Ozekmekci S., Apaydin H. et al. A hospital-based study: risk factors in development of motor complications in 555 Parkinson’s patients on levodopa therapy. Clin Neurol Neurosurg 2006; 108: 726–732. doi: 10.1016/j.clineuro.2006.02.002. PMID: 16564615.
- Rajput A.H. Levodopa prolongs life expectancy and is non-toxic to substantia nigra. Parkinsonism Relat Disord 2001; 8: 95–100. doi: 10.1016/s1353-8020(01)00023-2. PMID: 11489674.
- Schapira A.H., Bezard E., Brotchie J. et al. Novel pharmacological targets for the treatment of Parkinson’s disease. Nat Rev Drug Discov 2006; 5: 845–854. doi: 10.1038/nrd2087. PMID: 17016425.
- Lundblad M., Picconi B., Lindgren H., Cenci M.A. A model of L-DOPA-induced dyskinesia in 6-hydroxydopamine lesioned mice: relation to motor and cellular parameters of nigrostriatal function. Neurobiol Dis 2004; 16: 110–123. doi: 10.1016/j.nbd.2004.01.007. PMID: 15207268.
- Picconi B., Piccoli G., Calabresi P. Synaptic dysfunction in Parkinson’s disease. Adv Exp Med Biol 2012; 970: 553–572. doi: 10.1007/978-3-7091-0932-8_24. PMID: 22351072.
- Johnson K.A., Conn P.J., Niswender C.M. Glutamate receptors as therapeutic targets for Parkinson’s disease. CNS Neurol Disord Drug Targets 2009; 8: 475-491. doi: 10.2174/187152709789824606. PMID: 19702565.
- Niswender C.M., Conn P.J. Metabotropic glutamate receptors: physiology, pharmacology, and disease. Annu Rev Pharmacol Toxicol 2010; 50: 295–322. doi: 10.1146/annurev.pharmtox.011008.145533. PMID: 20055706.
- Nicoletti F., Bockaert J., Collingridge G.L. et al. Metabotropic glutamate receptors: from the workbench to the bedside. Neuropharmacology 2011; 60: 1017–1041. doi: 10.1016/j.neuropharm.2010.10.022. PMID: 21036182.
- Amalric M. Targeting metabotropic glutamate receptors (mGluRs) in Parkinson’s disease. Curr Opin Pharmacol 2015; 20: 29–34. doi: 10.1016/j.coph.2014.11.001. PMID: 25462289.
- Rylander D., Recchia A., Mela F. et al. Pharmacological modulation of glutamate transmission in a rat model of L-DOPA-induced dyskinesia: effects on motor behavior and striatal nuclear signaling. J Pharmacol Exp Ther 2009; 330: 227–235. doi: 10.1124/jpet.108.150425. PMID: 19357321.
- Breysse N., Baunez C., Spooren W. et al. Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism. J Neurosci 2002; 22: 5669–5678. DOI: 20026513. PMID: 12097518.
- Coccurello R., Breysse N., Amalric M. Simultaneous blockade of adenosine A2A and metabotropic glutamate mGlu5 receptors increase their efficacy in reversing Parkinsonian deficits in rats. Neuropsychopharmacology 2004; 29: 1451–1461. doi: 10.1038/sj.npp.1300444. PMID: 15039773.
- 74. Samadi P., Grégoire L., Morissette M. et al. Basal ganglia group II metabotropic glutamate receptors specific binding in non-human primate model of L-Dopa-induced dyskinesias. Neuropharmacology 2008; 54: 258–268. doi: 10.1016/j.neuropharm.2007.08.009. PMID: 18001807.
- Spooren W.P., Gasparini F., Bergmann R., Kuhn R. Effects of the prototypical mGlu(5) receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine on rotarod, locomotor activity and rotational responses in unilateral6-OHDA-lesioned rats. Eur J Pharmacol 2000; 406: 403–410. doi: 10.1016/s0014-2999(00)00697-x. PMID: 11040347.
- Gasparini F., Lingenhöhl K., Stoehr N. et al. 2-Methyl-6-(phenylethynyl)-pyridine (MPEP), a potent, selective and systemically active mGlu5 receptor antagonist. Neuropharmacology 1999; 38: 1493–1503. doi: 10.1016/s0028-3908(99)00082-9. PMID: 10530811.
- Ossowska K., Konieczny J., Wardas J. et al. An influence of ligands of metabotropic glutamate receptor subtypes on parkinsonian-like symptoms and the striatopallidal pathway in rats. Amino Acids 2007; 32: 179–188. doi: 10.1007/s00726-006-0317-y. PMID: 16699817.
- 78. Litim N., Morissette M., Di Paolo T. Metabotropic glutamate receptors as therapeutic targets in Parkinson’s disease: an update from the last 5 years of research. Neuropharmacology 2017; 115: 166-179. doi: 10.1016/j.neuropharm.2016.03.036. PMID: 27055772.
- Morin N., Grégoire L., Gomez-Mancilla B. et al. Effect of the metabotropic glutamate receptor type 5 antagonists MPEP and MTEP in parkinsonian monkeys. Neuropharmacology 2010; 58: 981–986. doi: 10.1016/j.neuropharm.2009.12.024. PMID: 20074579.
- 80. Maranis S., Stamatis D., Tsironis C., Konitsiotis S. Investigation of theantidyskinetic site of action of metabotropic and ionotropic glutamatereceptor antagonists. Intracerebral infusions in 6-hydroxydopamine-lesioned rats with levodopa-induced dyskinesia. Eur J Pharmacol 2012; 683: 71–77. doi: 10.1016/j.ejphar.2012.02.036. PMID: 22410193.
- Grégoire L., Morin N., Ouattara B. et al. The acute antiparkinsonian and antidyskinetic effect of AFQ056, a novel metabotropic glutamate receptor type 5 antagonist, in L-Dopa-treated parkinsonian monkeys. Parkinsonism Relat Disord 2011; 17: 270. doi: 10.1016/j.parkreldis.2011.01.008. PMID: 21315648.
- Bezard E., Pioli E.Y., Li Q. et al. The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model. Mov Disord 2014; 29: 1074–1079. doi: 10.1002/mds.25920. PMID: 24865335.
- Ko W.K., Pioli E., Li Q. et al. Combined fenobam and amantadine treatment promotes robust antidyskinetic effects in the 1-methyl-4-phenyl-1 2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson’s disease. Mov Disord 2014; 29: 772–779. doi: 10.1002/mds.25859. PMID: 24610195.
- Tison F., Keywood C., Wakefield M. et al. A phase 2A trial of the novel mGluR5-negative allosteric modulator dipraglurant for levodopa-induced dyskinesia in Parkinson’s disease. Mov Disord 2016; 31: 1373–1380. doi: 10.1002/mds.26659. PMID: 27214664.
- Chen L., Liu J., Ali U. et al. Chronic, systemic treatment with a metabotropic glutamate receptor 5 antagonist produces anxiolytic-like effects and reverses abnormal firing activity of projection neurons in the basolateral nucleus of the amygdala in rats with bilateral 6-OHDA lesions. Brain Res Bull 2011; 84: 215–223. doi: 10.1016/j.brainresbull.2011.01.005. PMID: 21255635.
- Hsieh M.H., Ho S.C., Yeh K.Y. et al. Blockade of metabotropic glutamate receptors inhibits cognition and neurodegeneration in an MPTP-induced Parkinson’s disease rat model. Pharmacol Biochem Behav 2012; 102: 64–71. doi: 10.1016/j.pbb.2012.03.022. PMID: 22487770.
- Masilamoni G.J., Bogenpohl J.W., Alagille D. et al. Metabotropic glutamate receptor 5 antagonist protects dopaminergic and noradrenergic neurons from degeneration in MPTP-treated monkeys. Brain 2011; 134: 2057–2073. doi: 10.1093/brain/awr137. PMID: 21705423.
- Alagarsamy S., Marino M.J., Rouse S.T. et al. Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems. Nat Neurosci 1999; 2: 234–240. doi: 10.1038/6338. PMID: 10195215.
- 89. Sala C., Roussignol G., Meldolesi J., Fagni L. Key role of the postsynaptic density scaffold proteins Shank and Homer in the functional architecture of Ca2+ homeostasis at dendritic spines in hippocampal neurons. J Neurosci 2005; 25: 4587–4592. doi: 10.1523/JNEUROSCI.4822-04.2005. PMID: 15872106.
- Pchitskaya E., Popugaeva E., Bezprozvanny I. Calcium signaling and molecular mechanisms underlying neurodegenerative diseases. Cell Calcium 2018; 70: 87–94. doi: 10.1016/j.ceca.2017.06.008. PMID: 28728834.
- Stefani IC., Wright D., Polizzi K.M., Kontoravdi C. The role of ER stress-induced apoptosis in neurodegeneration. Curr Alzheimer Res 2012; 9: 373–387. doi: 10.2174/156720512800107618. PMID: 22299619.
- Calì T., Ottolini D., Brini M. Calcium signaling in Parkinson's disease. Cell Tissue Res 2014; 357: 439–454. doi: 10.1007/s00441-014-1866-0. PMID: 24781149.
- Sun Y., Zhang H., Selvaraj S. et al. Inhibition of L-type Ca2+ channels by TRPC1-STIM1 complex is essential for the protection of dopaminergic neurons. J Neurosci 2017; 37: 3364–3377. doi: 10.1523/JNEUROSCI.3010-16.2017. PMID: 28258168.
- Bollimuntha S., Singh B.B., Shavali S. et al. TRPC1-mediated inhibition of 1-methyl-4-phenylpyridinium ion neurotoxicity in human SH-SY5Y neuroblastoma cells. J Biol Chem 2005; 280: 2132–2140. doi: 10.1074/jbc.M407384200. PMID: 15542611.
- Selvaraj S., Sun Y., Watt J.A. et al. Neurotoxin-induced ER stress in mouse dopaminergic neurons involves downregulation of TRPC1 and inhibition of AKT/mTOR signaling. J Clin Invest 2012; 122: 1354–1367. doi: 10.1172/JCI61332. PMID: 22446186.
- Chan C.S., Guzman J.N, Ilijic E. et al. 'Rejuvenation' protects neurons in mouse models of Parkinson's disease. Nature 2007; 447: 1081–1086. doi: 10.1038/nature05865. PMID: 17558391.
- McColgan P., Tabrizi S.J. Huntington's disease: a clinical review. Eur J Neurol 2018; 25: 24–34. doi: 10.1111/ene.13413. PMID: 28817209.
- Li S.H., Schilling G., Young W.S.3rd et al. Huntington’s disease gene (IT15) is widely expressed in human and rat tissues. Neuron 1993; 11: 985–993. doi: 10.1016/0896-6273(93)90127-d. PMID: 8240819.
- Strong T.V., Tagle D.A., Valdes J.M. et al. Widespread expression of the human and rat Huntington’s disease gene in brain and nonneural tissues. Nat Genet 1993; 5: 259–265. doi: 10.1038/ng1193-259. PMID: 8275091.
- Kim S.D., Fung V.S. An update on Huntington's disease: from the gene to the clinic. Curr Opin Neurol 2014; 27: 477–483. doi: 10.1097/WCO.0000000000000116. PMID: 24978638.
- Andre R., Carty L., Tabrizi S.J. Disruption of immune cell function by mutant huntingtin in Huntington's disease pathogenesis. Curr Opin Pharmacol 2016; 26: 33–38. doi: 10.1016/j.coph.2015.09.008. PMID: 26461267.
- Chen N., Luo T., Wellington C. et al. Subtype-specific enhancement of NMDA receptor currents by mutant huntingtin. J Neurochem 1999; 72: 1890–1898. doi: 10.1046/j.1471-4159.1999.0721890.x. PMID: 10217265.
- Schiefer J., Sprünken A., Puls C. et al. The metabotropic glutamate receptor 5 antagonist MPEP and the mGluR2 agonist LY379268 modify disease progression in a transgenic mouse model of Huntington’s disease. Brain Res 2004; 1019: 246–254. doi: 10.1016/j.brainres.2004.06.005. PMID: 15306259.
- Zeron M.M., Hansson O., Chen N. et al. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington’s disease. Neuron 2002; 33: 849–860. doi: 10.1016/s0896-6273(02)00615-3. PMID: 11906693.
- Raymond L.A. Striatal synaptic dysfunction and altered calcium regulation in Huntington disease. Biochem Biophys Res Commun 2017; 483: 1051–1062. doi: 10.1016/j.bbrc.2016.07.058. PMID: 27423394.
- Sun Y., Savanenin A., Reddy P.H., Liu Y.F. Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-d-aspartate receptors via post-synaptic density 95. J Biol Chem 2001; 276: 24713–24718. doi: 10.1074/jbc.M103501200. PMID: 11319238.
- Tang T.S., Tu H., Chan E.Y. et al. Huntingtin and huntingtin-associated protein 1influence neuronal calcium signaling mediated by inositol-(1 4,5)triphosphate receptor type 1. Neuron 2003; 39: 227–239. doi: 10.1016/s0896-6273(03)00366-0. PMID: 12873381.
- Doria J.G., Silva F.R., de Souza J.M. et al. Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington’s disease. Br J Pharmacol 2013; 169: 909–921. doi: 10.1111/bph.12164. PMID: 23489026.
- Nicodemo A.A., Pampillo M., Ferreira L.T. et al. Pyk2 uncouples metabotropic glutamate receptor G protein signaling but facilitates ERK1/2 activation. Mol Brain 2010; 3: 4. doi: 10.1186/1756-6606-3-4. PMID: 20180987.
- Humbert S., Bryson E.A., Cordelières F.P. et al. The IGF-1/Akt pathway is neuroprotective in Huntington’s disease and involves Huntingtin phosphorylation by Akt. Dev Cell 2002; 2: 831–837. doi: 10.1016/s1534-5807(02)00188-0. PMID: 12062094.
- Warby S.C., Doty C.N., Graham R.K. et al. Phosphorylation of huntingtin reduces the accumulation of its nuclear fragments. Mol Cell Neurosci 2009; 40: 121–127. doi: 10.1016/j.mcn.2008.09.007. PMID: 18992820.
- Chen T., Cao L., Dong W. et al. Protective effects of mGluR5 positive modulators against traumatic neuronal injury through PKC-dependent activation of MEK/ERK pathway. Neurochem Res 2012; 37: 983–990. doi: 10.1007/s11064-011-0691-z. PMID: 22228200.
- Loane D.J., Stoica B.A., Tchantchou F. et al. Novel mGluR5 positive allosteric modulator improves functional recovery, attenuates neurodegeneration, and alters microglial polarization after experimental traumatic brain injury. Neurotherapeutics 2014; 11: 857–869. doi: 10.1007/s13311-014-0298-6. PMID: 25096154.
- Zhang Y., Rodriguez A.L., Conn P.J. Allosteric potentiators of metabotropic glutamate receptor subtype 5 have differential effects on different signaling pathways in cortical astrocytes. J Pharmacol Exp Ther 2005; 15: 1212–1219. doi: 10.1124/jpet.105.090308. PMID: 16135701.
- Doria J.G., de Souza J.M., Andrade J.N. et al. The mGluR5 positive allosteric modulator CDPPB, ameliorates pathology and phenotypic signs of a mouse model of Huntington’s disease. Neurobiol Dis 2015; 73: 163–173. doi: 10.1016/j.nbd.2014.08.021. PMID: 25160573.
- Lessmann V., Gottmann K., Malcangio M. Neurotrophin secretion: current facts and future prospects. Prog Neurobiol 2003; 69: 341–374. doi: 10.1016/s0301-0082(03)00019-4. PMID: 12787574.
- Poo M.M. Neurotrophins as synaptic modulators. Nat Rev Neurosci 2001; 2: 24–32. doi: 10.1038/35049004. PMID: 11253356.
- Wu J., Shih H.P., Vigont V. et al. Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington's disease treatment. Chem Biol 2011; 18: 777-793. doi: 10.1016/j.chembiol.2011.04.012. doi: 10.1016/j.chembiol.2011.04.012. PMID: 21700213.
- Wu J., Ryskamp D.A., Liang X. et al. Enhanced store-operated calcium entry leads to striatal synaptic loss in a Huntington's disease mouse model. J Neurosci 2016; 36: 125–141. doi: 10.1523/JNEUROSCI.1038-15.2016. PMID: 26740655.
- Tang T.S., Guo C., Wang H. et al. Neuroprotective effects of inositol 1,4,5-trisphosphate receptor C-terminal fragment in a Huntington's disease mouse model. J Neurosci 2009; 29: 1257–1266. doi: 10.1523/JNEUROSCI.4411-08.2009. PMID: 19193873.
- Vigont V., Kolobkova Y., Skopin A. et al. Both Orai1 and TRPC1 are involved in excessive store-operated calcium entry in striatal neurons expressing mutant Huntingtin Exon 1. Front Physiol 2015; 6: 337. doi: 10.3389/fphys.2015.00337. PMID: 26635623.
- 122. Ryskamp D., Wu J., Geva M. et al. The sigma-1 receptor mediates the beneficial effects of pridopidine in a mouse model of Huntington disease. Neurobiol Dis 2017; 97: 46–59. doi: 10.1016/j.nbd.2016.10.006. PMID: 27818324
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