Mechanisms of control of neuron survival by the endocannabinoid system

Current Pharmaceutical Design

Volumn 14, Issue 23, 2008, Pages 2279-2288

  Galve Roperh, Ismael ^a   Aguado, Tania ^a   Palazuelos, Javier ^a   Guzmán, Manuel ^a  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

Author keywords

Cannabinoid; Endocannabinoid system; Neurodegeneration; Neurogenesis; Neuroinflammation; Neuron; Neuroprotection

Indexed keywords

2 ARACHIDONOYLGLYCEROL; ACYLGLYCEROL LIPASE; ANANDAMIDE; BRAIN DERIVED NEUROTROPHIC FACTOR; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CANNABINOID RECEPTOR AGONIST; CANNABINOID RECEPTOR ANTAGONIST; ENDOCANNABINOID; FATTY ACID AMIDASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN TYROSINE KINASE A; RIMONABANT; TUMOR NECROSIS FACTOR ALPHA CONVERTING ENZYME; VANILLOID RECEPTOR 1;

CELL DEATH; CELL SURVIVAL; DEGENERATIVE DISEASE; DRUG RECEPTOR BINDING; ENZYME ACTIVATION; HUMAN; INFLAMMATION; MICROGLIA; NERVE CELL; NERVE CELL PLASTICITY; NERVOUS SYSTEM DEVELOPMENT; NEURAL STEM CELL; NEUROINFLAMMATION; NEUROPROTECTION; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL SURVIVAL; ENDOCANNABINOIDS; HUMANS; NEURODEGENERATIVE DISEASES; NEUROGLIA; NEURONS; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, CANNABINOID, CB1; SIGNAL TRANSDUCTION;

EID: 52949118833     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161208785740117     Document Type: Review

References (120)

1. Gaoni Y, Mechoulam R. Isolation, structure and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 86: 1646-7.
2. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258: 1946-9.
3. Mechoulam R, Ben Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50: 83-90.
4. Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K, et al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biopbys Res Commun 1995; 215: 89-97.
5. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. Structure of a cannabinoid receptor, and functional expression of the cloned cDNA. Nature 1990; 346:561-4.
6. Munro S, Thomas KL, Abu Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61-5.
7. Freund TF, Katona I, Piomelli D. Role of endogenous cannabinoids in synaptic signaling. Physiol Rev 2003; 83: 1017-66.
8. Chevaleyre V, Takahashi KA, Castillo PE. Endocannabinoid-mediated synaptic plasticity in the CNS. Annu Rev Neurosci 2006; 29: 37-76.
9. Skaper SD, Buriani A, Dal Toso R, Petrelli L, Romanello S, Facci L, et al. The ALIAmide palmitoylethanolamide and cannabinoids, but not anandamide, are protective in a delayed postglutamate paradigm of excitotoxic death in cerebellar granule neurons. Proc Natl Acad Sci USA 1996; 93: 3984-9.
10. Shen M, Thayer SA. Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol Pharmacol 1998; 54: 459-62.
11. Nagayama T, Sinor AD, Simon RP, Chen J, Graham SH, Jin K, et al. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci 1999; 19: 2987-95.
12. Mechoulam R, Shohami E. Endocannabinoids and traumatic brain injury. Mol Neurobiol 2007; 36; 68-74.
13. van der Stelt M, Veldhuis WB, Bar PR, Veldink GA, Vliegenthart JF, Nicolay K. Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity. J Neurosci 2001; 21: 6475-9.
14. van der Stelt M, Veldhuis WB, van Haaften GW, Fezza F, Bisogno T, Bar PR, et al. Exogenous anandamide protects rat brain against acute neuronal injury in vivo. J Neurosci 2001; 21: 8765-71.
15. Veldhuis WB, van der Stelt M, Wadman MW, van Zadelhoff G, Maccarrone M, Fezza F, et al. Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxicity in the rat: role of vanilloid receptors and lipoxygenases. J Neurosci 2003; 23: 4127-33.
16. Panikashvili D, Simeonidou C, Ben-Shabat S, Hanus L, Breuer A, Mechoulam R, et al. An endogenous cannabinoid (2-AG) is neuro-protective after brain injury. Nature 2001; 413: 527-31.
17. Fernandez-Lopez D, Martinez-Orgado J, Nunez E, Romero J, Lorenzo P, Moro MA, et al. Characterization of the neuroprotective effect of the cannabinoid agonist WIN-55212 in an in vitro model of hypoxic-ischemic brain damage in newborn rats. Pediatr Res 2006; 60: 169-73.
18. Mangieri RA, Piomelli D. Enhancement of endocannabinoid signaling and the pharmacotherapy of depression. Pharmacol Res 2007; 56: 360-6.
19. Karanian DA, Brown QB, Makriyannis A, Kosten TA, Bahr BA. Dual modulation of endocannabinoid transport and fatty acid amide hydrolase protects against excitotoxicity. J Neurosci 2005; 25: 7813-20.
20. Zani A, Braida D, Capurro V, Sala M. Delta9-tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors. Br J Pharmacol 2007; 152: 1301-11.
21. Kathuria S, Gaetani S, Fegley D, Valino F, Duranti A, Tontini A, et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med 2003; 9: 76-81.
22. Parmentier-Batteur S, Jin K, Mao XO, Xie L, Greenberg DA. Increased severity of stroke in CB1 cannabinoid receptor knock-out mice. J Neurosci 2002; 22: 9771-5.
23. Marsicano G, Goodenough S, Monory K, Hermann H, Eder M, Cannich A, et al. CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science 2003; 302: 84-8.
24. Bilkei-Gorzo, A, Racz I, Valverde O, Otto M, Michel K, Sastre M, et al. Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. Proc Natl Acad Sci USA 2005; 102: 15670-5.
25. Monory K, Massa F, Egertova M, Eder M, Blaudzun H, Westenbroek R, et al. The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 2006; 51: 455-661.
26. Pintor A, Tebano MT, Martire A, Grieco R, Galluzo, M, Scattoni ML, et al. The cannabinoid receptor agonist WIN 55,212-2 attenuates the effects induced by quinolinic acid in the rat striatum. Neuropharmacology 2006; 51: 1004-12.
27. Shouman B, Fontaine RH, Baud O, Schwendimann L, Keller M, Spedding M, et al. Endocannabinoids potently protect the newborn brain against AMPA-kainate receptor-mediated excitotoxic damage. Br J Pharmacol 2006; 148: 442-51.
28. Melis M, Pillolla G, Bisogno T, Minassi A, Petrosina S, Perra S, et al. Protective activation of the endocannabinoid system during ischemia in dopamine neurons. Neurobiol Dis 2006; 24: 15-27.
29. Guan XL, He X, Ong WY, Yeo WK, Shui G, Wenk MR. Non-targeted profiling of lipids during kainate-induced neuronal injury. FASEB J 2006; 20: 1152-61.
30. Hansen H, Moesgaard B, Petersen G. Putative neuroprotective actions of N-acyl-ethanolamines. Pharmacol Ther 2002; 95: 119.
31. Franklin A, Parmentier-Batteur S, Walter L, Greenberg DA, Stella N. Palmitoylethanolamide increases after focal cerebral ischemia and potentiates microglial cell motility. J Neurosci 2003; 23: 7767-75.
32. Berger C, Schmid PC, Schabitz WR, Wolf M, Schwab S, Schmid HH. Massive accumulation of N-acylethanolamines after stroke. Cell signalling in acute cerebral ischemia? J Neurochem, 2004; 88: 1159-67.
33. Jin KL, Mao XO, Goldsmith PC, Greenberg DA. CB1 cannabinoid receptor induction in experimental stroke. Ann Neurol 2000; 48: 257-61.
34. Aguado T, Romero E, Monory K, Palazuelos J, Sendtner M, Marsicano G, et al. The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis. J Biol Chem 2007; 282: 23892-8.
35. Clement AB, Hawkins EG, Lichtman AH, Cravatt BF. Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. J Neurosci 2003; 23: 3916-23.
36. Zhao C, Deng W, Gage FH. Mechanisms and functional implications of adult neurogenesis. Cell 2008; 132: 645-60.
37. Gould E. How widespread is adult neurogenesis in mammals? Nat Rev Neurosci 2007; 8: 481-8.
38. Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E. Neurogenesis in the adult is involved in the formation of trace memories. Nature 2001; 410: 372-6.
39. Guillemot F. Cell fate specification in the mammalian telencephalon. Prog Neurobiol 2007; 83: 37-52.
40. Harkany T, Guzman M, Galve-Roperh I, Berghuis P, Devi LA, Mackie K. The emerging functions of endocannabinoid signaling during CNS development. Trends Pharmacol Sci 2007; 28: 83-92.
41. Galve-Roperh I, Aguado T,. Palazuelos J, Guzman M. The endocannabinoid system and neurogenesis in health and disease. Neuroscientist 2007; 13: 109-14.
42. Pacher P, Batkai S, Kunos G. The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol Rev 2006; 58: 389-462.
43. Jin K, Xie L, Kim SH, Parmentier-Batteur S, Sun Y, Mao XO, et al. Defective adult neurogenesis in CB1 cannabinoid receptor knockout mice. Mol Pharmacol 2004; 66: 204-8.
44. Aguado T, Monory K, Palazuelos J, Stella N, Cravatt B, Lutz B, et al. The endocannabinoid system drives neural progenitor proliferation. FASEB J 2005; 19: 1704-6.
45. Palazuelos J, Aguado T, Egia A, Mechoulam R, Guzman M, Galve-Roperh I. Non-psychoactive CB2 cannabinoid agonists stimulate neural progenitor proliferation. FASEB J 2006; 20: 2405-7.
46. Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, et al. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects. J Clin Invest 2005; 115: 3104-16.
47. Aguado T, Palazuelos J, Monory K, Stella N, Cravatt B, Lutz B, et al. The endocannabinoid system promotes astroglial differentiation by acting on neural progenitor cells. J Neurosci 2006; 26: 1551-61.
48. Kim D, Thayer SA. Cannabinoids inhibit the formation of new synapses between hippocampal neurons in culture. J Neurosci 2001; 21: RC146.
49. Rueda D, Navarro B, Martinez-Serrano A, Guzman M, Galve-Roperh I. The endocannabinoid anandamide inbibits neuronal progenitor cell differentiation through attenuation of the RAP1/B-RAF/ERK pathway. J Biol Chem 2002; 16: 16.
50. Molina-Holgado F, Rubio-Araiz A, Garcia-Ovejero D, Williams RJ, Moore JD, Arevalo-Martin A, et al. CB2 cannabinoid receptors promote mouse neural stem cell proliferation. Eur J Neurosci 2007; 25: 629-34.
51. Molina-Holgado F, Pinteaux E, Heenan L, Moore JD, Rothwell NJ, Gibson RM. Neuroprotective effects of the synthetic cannabinoid HU-210 in primary cortical neurons are mediated by phosphatidylinositol 3-kinase/ AKT signaling. Mol Cell Neurosci 2005; 28: 189-94.
52. Ozaita A, Puighermanal E, Maldonado R. Regulation of PI3K/Akt/GSK-3 pathway by cannabinoids in the brain. J Neurochem 2007; 102: 1105-14.
53. Gomez del Pulgar T, Velasco G, Guzman M. The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt. Biochem J 2000; 347: 369-73.
54. Gomez Del Pulgar T, De Ceballos ML, Guzman M, Velasco G. Cannabinoids protect astrocytes from ceramide-induced apoptosis through the phosphatidylinositol 3-kinase/protein kinase B pathway. J Biol Chem 2002; 277: 36527-33.
55. Molina-Holgado E, Vela JM, Arevalo-Martin A, Almazan G, Molina-Holgado F, Borrell J, et al. Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 2002; 22: 9742-53.
56. Galve-Roperh I, Rueda D, Gomez Del Pulgar T, Velasco G, Guzman M. Mechanism of extracellular signal-regulated kinase activation by the CB1 cannabinoid receptor. Mol Pharmacol 2002; 62: 1385-92.
57. Hart S, Fischer OM, Ullrich A. Cannabinoids induce cancer cell proliferation via tumor necrosis factor alpha-converting enzyme (TACE/ADAM17)-mediated transactivation of the epidermal growth factor receptor. Cancer Res 2004; 64: 1943-50.
58. Derkinderen P, Valjent E, Toutant M, Corvol JC, Enslen H, Ledent C, et al. Regulation of extracellular signal-regulated kinase by cannabinoids in hippocampus. J Neurosci 2003; 23: 2371-82.
59. Valjent E, Pages C, Rogard M, Besson MJ, Maldonado R, Caboche J. Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission. Eur J Neurosci 2001; 14: 342-52.
60. Moranta D, Esteban S, Garcia-Sevilla JA. Acute, chronic and withdrawal effects of the cannabinoid receptor agonist WIN55212-2 on the sequential activation of MAPK/Raf-MEK-ERK signaling in the rat cerebral frontal cortex: short-term: regulation by intrinsic and extrinsic pathways. J Neurosci Res 2007; 85: 656-67.
61. Tonini R, Ciardo S, Cerovic M, Rubino T, Parolaro D, Mazzanti M, et al. ERK-dependent modulation of cerebellar synaptic plasticity after chronic Delta9-tetrahydrocannabinol exposure. J Neurosci 2006; 26: 5810-8.
62. Bouaboula M, Poinot-Chazel C, Bourrie B, Canat X, Calandra B, Rinaldi-Carmona M, et al. Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 1995; 312: 637-41.
63. Sanchez C, Galve-Roperh I, Rueda D, Guzman M. Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the Delta9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. Mol Pharmacol 1998; 54: 834-43.
64. Davis MI, Ronesi J, Lovinger DM. A predominant role for inhibition of the adenylate cyclase/protein kinase A pathway in ERK activation by cannabinoid receptor 1 in N1E-115 neuroblastoma cells. J Biol Chem 2003; 278: 48973-80.
65. Kim SH, Won SJ, Mao XO, Jin K, Greenberg DA. Molecular mechanisms of cannabinoid protection from neuronal excitotoxicity. Mol Pharmacol 2006; 69: 691-6.
66. Porcella A, Gessa GL, Pani L. Delta9-tetrahydrocannabinol increases sequence-specific AP-1 DNA-binding activity and Fos-related antigens in the rat brain. Eur J Neurosci 1998; 10: 11743-51.
67. Zhao Q, He Z, Chen N, Cho YY, Zhu F, Lu C, et al. 2-Arachidonoylglycerol stimulates activator protein-1-dependent transcriptional activity and enhances epidermal growth factor-induced cell transformation in JB6 P+ cells. J Biol Chem 2005; 280: 26735-42.
68. Bouaboula M, Bourrie B, Rinaldi Carmona M, Shire D, Le Fur G, Casellas P. Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. J Biol Chem 1995b; 270: 13973-80.
69. Dorsam RT, Gutkind JS. G-protcin-coupled receptors and cancer. Nat Rev Cancer 2007; 7: 79-94.
70. Jordan JD, He JC, Eungdamrong NJ, Gomes I, Ali W, Nguyen T, et al. Cannabinoid receptor-induced neurite outgrowth is mediated by Rap1 activation through G(alpha)o/i-triggered proteasomal degradation of Rap1GAPII. J Biol Chem 2005; 280: 11413-21.
71. Preet A, Gauju RK, Groopman JE. Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene 2008; 27: 339-46.
72. Rubovitch V, Gafni M, Sarne Y. The involvement of VEGF receptors and MAPK in the cannabinoid potentiation of Ca2+ flux into N18TG2 neuroblastoma cells. Brain Res Mol Brain Res 2004; 120: 138-44.
73. Khaspekov LG, Brenz Verca MS, Frumkina LE, Hermann H, Marsicano G, Lutz B. Involvement of brain-derived neurotrophic factor in cannabinoid receptor-dependent protection against excitotoxicity. Eur J Neurosci 2004; 19: 1691-8.
74. De March Z, Zuccato C, Giampa C, Patassini S, Bari M, Gasperi V, et al. Cortical expression of brain derived neurotrophic factor and type-1 cannabinoid receptor after striatal excitotoxic lesions. Neuroscience 2008; 152: 734-40.
75. Berghuis P, Dobszay MB, Wang X, Spano S, Ledda F, Sousa KM, et al. Endocannabinoids regulate interneuron migration and morphogenesis by transactivating the TrkB receptor. Proc Natl Acad Sci USA 2005; 102: 19115-20.
76. Williams EJ, Walsh FS, Doherty P. The FGF receptor uses the endocannabinoid signaling system to couple to an axonal growth response. J Cell Biol 2003; 160: 481-6.
77. Pryce G, Baker D. Emerging properties of cannabinoid medicines in management of multiple sclerosis. Trends Neurosci 2005; 28: 272-6.
78. Pertwee RG. Cannabinoids and multiple sclerosis. Mol Neurobiol 2007; 36: 45-59.
79. Pryce G, Ahmed Z, Hankey DJ, Jackson SJ, Croxford JL, Pocock JM, et al. Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 2003; 126: 2191-202.
80. Maresz K, Pryce G, Ponomarev ED, Marsicano G, Croxford JL, Shriver LP, et al. Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat Med 2007; 13: 492-7.
81. Arevalo-Martin A, Vela JM, Molina-Holgado E, Borrell J, Guaza C. Therapeutic action of cannabinoids in a murine model of multiple sclerosis. J Neurosci 2003; 23: 2511-6.
82. Palazuelos J, Davoust N, Julien B, Hatterer E, Aguado T, Mechoulam R, et al. The CB2 cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis. J Biol Chem 2008; 283: 13320-9.
83. Ni X, Geller EB, Eppihimer MJ, Eisenstein TK, Adler MW, Tuma RF. Win 55212-2, a cannabinoid receptor agonist, attenuates leukocyte/ endothelial interactions in an experimental autoimmune encephalomyelitis model. Mult Scler 2004; 10: 158-64.
84. Zhang M, Martin BF, Adler MW, Razdan RK, Jallo JI, Tuma RF. Cannabinoid CB2 receptor activation decreases cerebral infarction in a mouse focal ischemia/reperfusion model. J Cereb Blood Flow Metab 2007; 27: 1387-96.
85. Docagne F, Muneton V, Clemente D, Ali C, Loria F, Correa F, et al. Excitotoxicity in a chronic model of multiple sclerosis: Neuroprotective effects of cannabinoids through CB1 and CB2 receptor activation. Mol Cell Neurosci 2007; 34: 551-61.
86. Fernandez-Ruiz J, Romero J, Velasco G, Tolon RM, Ramos JA, Guzman M. Cannabinoid CB2 receptor: a new target for controlling neural cell survival? Trends Pharmacol Sci 2007; 28: 39-45.
87. Marcsz K, Carrier EJ, Ponomarev ED, Hillard CJ, Dittel BN. Modulation of the cannabinoid CB2 receptor in microglial cells in response to inflammatory stimuli. J Neurochem 2005; 95: 437-45.
88. Benito C, Romero JP, Tolon RM, Clemente D, Docagne F, Hillard CJ, et al. Cannabinoid CB1 and CB2 receptors and fatty acid amide hydrolase are specific markers of plaque cell subtypes in human multiple sclerosis. J Neurosci 2007; 27: 2396-402.
89. Ramirez BG, Blazquez C, Gomez del Pulgar T, Guzman M, de Ceballos ML. Prevention of Alzheimer's disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J Neurosci 2005; 25: 1904-13.
90. Witting A, Chen L, Cudaback E, Straiker A, Walter L, Rickman B, et al. Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection. Proc Natl Acad Sci USA 2006; 103: 6362-7.
91. Eljaschewitsch E, Witting A, Mawrin C, Lee T, Schmidt PM, Wolf S, et al. The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. Neuron 2006; 49: 67-79.
92. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 2007; 10: 1387-94.,
93. Davoust N, Vuailat C, Cavillon G, Domenget C, Hatterer E, Bernard A, et al. Bone marrow CD34+/B220+ progenitors target the inflamed brain and display in vitro differentiation potential toward microglia. FASED J 2006; 20: 2081-92.
94. Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-) Delta9-tetrahydrocannabunol are neuroprotective antioxidants. Proc Natl Acad Sci USA 1998; 95: 8269-73.
95. Marsicano G, Moosmann B, Hermann H, Lutz B, Behlt C. Neuroprotective properties of camabinoids against oxidative stress: role of the cannabinoid receptor CB1. J Neurochem 2002; 80: 448-56.
96. Hayakawa K, Mishima K, Nozako M, Hazekawa M, Irie K, Fujioka M, et al. Delayed treatment with cannabidiol has a cerebroprotective action via, a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism. J Neurochem 2007; 102: 1488-96.
97. Lastres-Becker I, Molina-Holgado F, Ramos JA, Mechoulam R, Fernandez-Ruiz J. Cannabinoids provide neuroprotection against 6-hydroxydopamine toxicity in vivo and in vitro: Relevance to Parkinson's disease. Neurobiol Dis 2005; 19: 96-107.
98. Kozak M Crews BC, Morrow JD, Wang LH, Ma YH, Weinander R, et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 2002; 277: 44877-85.
99. Sang N, Zhang J, Chen C. PGE2 glycerol ester, a COX-2 oxidative metabolite of 2-arachidonoyl glycerol, modulates inhibitory synaptic transmission in mouse hippocampal neurons. J Physiol 2006; 572: 735-45.
100. Correa F, Docagne F, Clemente D, Mestre L, Becker C, Guaza C. Anandamide inhibits IL-12p40 production by acting on the promoter repressor element GA-12: possible involvement of the COX-2 metabolite prostamide E2. Biochem J 2008; 409: 761-70.
101. Matas D, Juknat A, Pietr M, Klin Y, Vogel Z. Anandamide protects from low serum-induced apoptosis via its degradation to ethanolamine. J Biol Chem 2007; 282: 7885-92.
102. Lo Vernic J, Fu J, Astarita G, LaRana G, Russo R, Caliguano A, et al. The nuclear receptor peroxisome proliferator-activated roceptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol 2005; 67: 15-9.
103. Ryberg E, Larsson N, Sjogren S, Hjorth S, Hermansson NO, Leonova J, et al. The orphan receptor GPR55 is a novel cannabinoid receptor. Br J Pharmacol 2007; 152: 1092-101.
104. Sun Y, Alexander SP, Garle MJ, Gibson CL, Hewitt K, Murphy SP, et al. Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism. Br J Pharmacol 2007; 152: 734-43.
105. Maccarrone M, Finazzi-Agro A. Yhc endocannabinoid system, anandamide and the regulation of mammalian cell apoptosis. Cell Death Differ 2003; 10: 946-55.
106. Cernak I, Vink R, Natale J, Stoica B, Lea PMt, Movsesyan V, et al. The "dark side" of endocannabinoids: a neurotoxic role for anandamide. J Cereb Blood Flow Metab 2004; 24: 564-78.
107. Bari M, Battista N, Fezza F, Finazzi-Agro A, Maccarrone M. Lipid rafts control signaling of type-1 cannabiuoid receptors in neuronal cells. Implications for anandamide-induced apoptosis. J Biol Chem 2005; 280: 12212-20.
108. Hansen HH, Azeoitia I, Pons S, Romero J, Garcia-Segura LM, Ramos JA, et al. Blockade of cannabinoid CB1 receptor function protects against in vivo disseminating brain damage following NMDA-induced excitotoxicity. J Neurochem 2002; 82: 154-8.
109. Pegorini S, Zani A, Braida D, Guerini-Rocco C, Sala M. Vanilloid VR1 receptor is involved in rimonabant-induced neuroprotection. Br J Pharmacol 2006; 147: 552-9.
110. Muthian S, Rademacher DJ, Roelke CT, Gross GJ, Hillard CJ. Anandamide content is increased and CB1 cannabinoid receptor blockade is protective during transient, focal cerebral ischemia. Neuroscience 2004; 129: 743-50.
111. Chan GC, Hinds TR, Impey S, Storm DR. Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. J Neurosci 1998; 18: 5322-32.
112. Downer EJ, Fogarty MP, Campbell VA. Tetrahydrocannabinol-induced neurotoxicity depends on CB1 receptor-mediated c-Jun N-terminal kinase activation in cultured cortical neurons. Br J Pharmacol 2003; 140: 547-57.
113. Derkinderen P, Ledent C, Parmentier M, Girault JA. Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors in hippocampus. J Neurochem 2001; 77: 957-60.
114. Movsesyan VA, Stoica BA, Yakoviev AG, Knoblach SM, Lea PM, Cernak I, et al. Anandamide-induced cell death in primary neuronal cultures: role of calpain and caspase pathways. Cell Death Differ 2004; 11: 1121-32.
115. Gowran A, Campbell VA. A role for p53 in the regulation of lysosomal permeability by delta9-tetrahydrocannabinol in rat cortical neurones: implications for neurodegeneration. J Neurochem 2008; 105: 1513-24.
116. Mestre L, Correa F, Docagne F, Clemente D, Guaza C. The synthetic cannabinoid WIN 55,212-2 increases COX-2 expression and PGE2 release in murine brain-derived endothelial cells following Theiler's virus infection. Biochem Pharmacol 2006; 72: 869-80.
117. Ramer R, Weinzierl U, Schwind B, Brune K, Hinz B. Ceramide is involved in r(+)-Methanandamide-induced cyclooxygenase-2 expression in human neuroglioma cells. Mol Pharmacol 2003; 64: 1189-98.
118. Borsello T, Forloni G. JNK signalling: a possible target to prevent neurodegeneration. Curr Pharm Des 2007; 13(18): 1975-86.
119. Hagg T. Endogenous regulators of adult CNS neurogenesis. Curr Pharm Des 2007; 13(18): 1829-40.
120. Sharma HS, Sjoquist PO, Ali SF. Drugs of Abuse-induced hyperthermia, blood-brain barrier dysfunction and neurotoxicity: neuroprotective effects of a new antioxidant compound H-290/51. Curr Pharm Des 2007; 13(18): 1903-23.