Neuroprotective roles of pituitary adenylate cyclase-activating polypeptide in neurodegenerative diseases

BMB Reports

Volumn 47, Issue 7, 2014, Pages 369-375

  Lee, Eun Hye ^a   Seo, Su Ryeon ^a  

^a Kangwon National University   (South Korea)

Author keywords

Alzheimer's disease (AD); Cerebral ischemia; Neurodegeneration; Parkinson's disease (PD); Pituitary adenylate cyclase activating polypeptide (PACAP38); Traumatic brain injury (TBI)

Indexed keywords

HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE RECEPTOR; REACTIVE OXYGEN METABOLITE;

ALZHEIMER DISEASE; BRAIN INJURY; BRAIN ISCHEMIA; DEGENERATIVE DISEASE; HUMAN; METABOLISM; PARKINSON DISEASE; PATHOLOGY; SIGNAL TRANSDUCTION;

ALZHEIMER DISEASE; BRAIN INJURIES; BRAIN ISCHEMIA; HUMANS; NEURODEGENERATIVE DISEASES; PARKINSON DISEASE; PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE; REACTIVE OXYGEN SPECIES; RECEPTORS, PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE; SIGNAL TRANSDUCTION;

EID: 84905911804     PISSN: 19766696     EISSN: 1976670X     Source Type: Journal    
DOI: 10.5483/BMBRep.2014.47.7.086     Document Type: Short Survey

References (87)

1. Miyata, A., Arimura, A., Dahl, R. R., Minamino, N., Uehara, A., Jiang, L., Culler, M. D. and Coy, D. H. (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem. Biophys. Res. Commun. 164, 567-574.
2. Läuffer, J. M., Modlin, I. M. and Tang, L. H. (1999) Biological relevance of pituitary adenylate cyclase-activating polypeptide (PACAP) in the gastrointestinal tract. Regul. Pepti. 84, 1-12.
3. Journot, L., Spengler, D., Pantaloni, C., Dumuis, A., Sebben, M. and Bockaert, J. (1994) The PACAP receptor: Generation by alternative splicing of functional diversity among G protein-coupled receptors in nerve cells. Semin. Cell Dev. Biol. 5, 263-272.
4. Pantaloni, C., Brabet, P., Bilanges, B., Dumuis, A., Houssami, S., Spengler, D., Bockaert, J. and Journot, L. (1996) Alternative splicing in the N-terminal extracellular domain of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor modulates receptor selectivity and relative potencies of PACAP-27 and PACAP-38 in phospholipase C activation. J. Biol. Chem. 271, 22146-22151.
5. Hosoya, M., Onda, H., Ogi, K., Masuda, Y., Miyamoto, Y., Ohtaki, T., Okazaki, H., Arimura, A. and Fujino, M. (1993) Molecular cloning and functional expression of rat cDNAs encoding the receptor for pituitary adenylate cyclase activating polypeptide (PACAP). Biochem. Biophys. Res. Commun. 194, 133-143.
6. Spengler, D., Waeber, C., Pantaloni, C., Holsboer, F., Bockaert, J., Seeburg, P. H. and Journot, L. (1993) Differential signal transduction by five splice variants of the PACAP receptor. Nature 365, 170-175.
7. Harmar, A. J. (2001) Family-B G-protein-coupled receptors. Genome Biol. 2, REVIEWS393.1-3013.10.
8. Arimura, A., Somogyvari-Vigh, A., Weill, C., Fiore, R. C., Tatsuno, I., Bay, V. and Brenneman, D. E. (1994) PACAP functions as a neurotrophic factor. Ann. N. Y. Acad. Sci. 739, 228-243.
9. Hannibal, J. (2002) Pituitary adenylate cyclase-activating peptide in the rat central nervous system: an immunohistochemical and in situ hybridization study. J. Comp. Neurol. 453, 389-417.
10. Sundler, F., Ekblad, E., Hannibal, J., Moller, K., Zhang, Y. Z., Mulder, H., Elsas, T., Grunditz, T., Danielsen, N., Fahrenkrug, J. and Uddman, R. (1996) Pituitary adenylate cyclase-activating peptide in sensory and autonomic ganglia: localization and regulation. Ann. N. Y. Acad. Sci. 805, 410-426; discussion 427-428.
11. Gonzalez, B. J., Basille, M., Vaudry, D., Fournier, A. and Vaudry, H. (1997) Pituitary adenylate cyclase-activating polypeptide promotes cell survival and neurite outgrowth in rat cerebellar neuroblasts. Neuroscience 78, 419-430.
12. Vaudry, D., Gonzalez, B. J., Basille, M., Yon, L., Fournier, A. and Vaudry, H. (2000) Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol. Rev. 52, 269-324.
13. Lioudyno, M., Skoglosa, Y., Takei, N. and Lindholm, D. (1998) Pituitary adenylate cyclase-activating polypeptide (PACAP) protects dorsal root ganglion neurons from death and induces calcitonin gene-related peptide (CGRP) immunoreactivity in vitro. J. Neurosci. Res. 51, 243-256.
14. Morio, H., Tatsuno, I., Hirai, A., Tamura, Y. and Saito, Y. (1996) Pituitary adenylate cyclase-activating polypeptide protects rat-cultured cortical neurons from glutamate-induced cytotoxicity. Brain Res. 741, 82-88.
15. Chen, Y., Samal, B., Hamelink, C. R., Xiang, C. C., Chen, M., Vaudry, D., Brownstein, M. J., Hallenbeck, J. M. and Eiden, L. E. (2006) Neuroprotection by endogenous and exogenous PACAP following stroke. Regul. Pept. 137, 4-19.
16. Tanaka, J., Koshimura, K., Murakami, Y., Sohmiya, M., Yanaihara, N. and Kato, Y. (1997) Neuronal protection from apoptosis by pituitary adenylate cyclase-activating polypeptide. Regul. Pept. 72, 1-8.
17. Waschek, J. A. (2002) Multiple actions of pituitary adenylyl cyclase activating peptide in nervous system development and regeneration. Dev. Neurosci. 24, 14-23.
18. Waschek, J. A. (2013) VIP and PACAP: neuropeptide modulators of CNS inflammation, injury, and repair. Br. J. Pharmacol. 169, 512-523.
19. May, V., Lutz, E., MacKenzie, C., Schutz, K. C., Dozark, K. and Braas, K. M. (2010) Pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1HOP1 receptor activation coordinates multiple neurotrophic signaling pathways: Akt activation through phosphatidylinositol 3-kinase gamma and vesicle endocytosis for neuronal survival. J. Biol. Chem. 285, 9749-9761.
20. Dejda, A., Sokolowska, P. and Nowak, J. Z. (2005) Neuroprotective potential of three neuropeptides PACAP, VIP and PHI. Pharmacol. Rep. 57, 307-320.
21. Shoge, K., Mishima, H. K., Saitoh, T., Ishihara, K., Tamura, Y., Shiomi, H. and Sasa, M. (1999) Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons. Brain Res. 839, 66-73.
22. Pugh, P. C. and Margiotta, J. F. (2006) PACAP support of neuronal survival requires MAPK- and activity-generated signals. Mol. Cell. Neurosci. 31, 586-595.
23. Villalba, M., Bockaert, J. and Journot, L. (1997) Pituitary adenylate cyclase-activating polypeptide (PACAP-38) protects cerebellar granule neurons from apoptosis by activating the mitogen-activated protein kinase (MAP kinase) pathway. J. Neurosci. 17, 83-90.
24. Vaudry, D., Gonzalez, B. J., Basille, M., Pamantung, T. F., Fontaine, M., Fournier, A. and Vaudry, H. (2000) The neuroprotective effect of pituitary adenylate cyclase-activating polypeptide on cerebellar granule cells is mediated through inhibition of the CED3-related cysteine protease caspase-3/CPP32. Proc. Natl. Acad. Sci. U. S. A. 97, 13390-13395.
25. Frechilla, D., Garcia-Osta, A., Palacios, S., Cenarruzabeitia, E. and Del Rio, J. (2001) BDNF mediates the neuroprotective effect of PACAP-38 on rat cortical neurons. Neuroreport 12, 919-923.
26. Falluel-Morel, A., Aubert, N., Vaudry, D., Basille, M., Fontaine, M., Fournier, A., Vaudry, H. and Gonzalez, B. J. (2004) Opposite regulation of the mitochondrial apoptotic pathway by C2-ceramide and PACAP through a MAP-kinase-dependent mechanism in cerebellar granule cells. J. Neurochem. 91, 1231-1243.
27. Bhave, S. V. and Hoffman, P. L. (2004) Phosphatidylinositol 3'-OH kinase and protein kinase A pathways mediate the anti-apoptotic effect of pituitary adenylyl cyclase-activating polypeptide in cultured cerebellar granule neurons: modulation by ethanol. J. Neurochem. 88, 359-369.
28. Delgado, M. and Ganea, D. (2003) Vasoactive intestinal peptide prevents activated microglia-induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma. FASEB J. 17, 1922-1924.
29. Gottschall, P. E., Tatsuno, I. and Arimura, A. (1994) Regulation of interleukin-6 (IL-6) secretion in primary cultured rat astrocytes: synergism of interleukin-1 (IL-1) and pituitary adenylate cyclase activating polypeptide (PACAP). Brain Res. 637, 197-203.
30. Ohtaki, H., Nakamachi, T., Dohi, K., Aizawa, Y., Takaki, A., Hodoyama, K., Yofu, S., Hashimoto, H., Shintani, N., Baba, A., Kopf, M., Iwwakura, Y., Matsuda, K., Arimura, A. and Shioda, S. (2006) Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6. Proc. Natl. Acad. Sci. U. S. A. 103, 7488-7493.
31. Dejda, A., Seaborn, T., Bourgault, S., Touzani, O., Fournier, A., Vaudry, H. and Vaudry, D. (2011) PACAP and a novel stable analog protect rat brain from ischemia: Insight into the mechanisms of action. Peptides. 32, 1207-1216.
32. Banks, W. A., Uchida, D., Arimura, A., Somogyvari-Vigh, A. and Shioda, S. (1996) Transport of pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier and the prevention of ischemia-induced death of hippocampal neurons. Ann. N. Y. Acad. Sci. 805, 270-277; discussion 277-279.
33. Uchida, D., Arimura, A., Somogyvári-Vigh A, Shioda, S. and Banks, W. A. (1996) Prevention of ischemia-induced death of hippocampal neurons by pituitary adenylate cyclase activating polypeptide. Brain Res. 736, 280-286.
34. Reglodi, D., Somogyvari-Vigh, A., Vigh, S., Kozicz, T. and Arimura, A. (2000) Delayed systemic administration of PACAP38 is neuroprotective in transient middle cerebral artery occlusion in the rat. Stroke 31, 1411-1417.
35. Stetler, R. A., Gao, Y., Zukin, R. S., Vosler, P. S., Zhang, L., Zhang, F., Cao, G., Bennett, M. V. and Chen, J. (2010) Apurinic/apyrimidinic endonuclease APE1 is required for PACAP-induced neuroprotection against global cerebral ischemia. Proc. Natl. Acad. Sci. U. S. A. 107, 3204-3209.
36. Shintani, N., Suetake, S., Hashimoto, H., Koga, K., Kasai, A., Kawaguchi, C., Morita, Y., Hirose, M., Sakai, Y., Tomimoto, S., Matsuda, T. and Bada, A. (2005) Neuroprotective action of endogenous PACAP in cultured rat cortical neurons. Regul. Pept. 126, 123-128.
37. Vaudry, D., Pamantung, T. F., Basille, M., Rousselle, C., Fournier, A., Vaudry, H., Beauvillain, J. C. and Gonzalez, B. J. (2002) PACAP protects cerebellar granule neurons against oxidative stress-induced apoptosis. Eur. J. Neurosci. 15, 1451-1460.
38. Horvath, G., Reglodi, D., Opper, B., Brubel, R., Tamas, A., Kiss, P., Toth, G., Csernus, V., Matkovits, A. and Racz, B. (2010) Effects of PACAP on the oxidative stress-induced cell death in chicken pinealocytes is influenced by the phase of the circadian clock. Neurosci. Lett. 484, 148-152.
39. Armstrong, B. D., Abad, C., Chhith, S., Cheung-Lau, G., Hajji, O. E., Nobuta, H. and Waschek, J. A. (2008) Impaired nerve regeneration and enhanced neuroinflammatory response in mice lacking pituitary adenylyl cyclase activating peptide. Neuroscience 151, 63-73.
40. Suk, K., Park, J. H. and Lee, W. H. (2004) Neuropeptide PACAP inhibits hypoxic activation of brain microglia: a protective mechanism against microglial neurotoxicity in ischemia. Brain Res. 1026, 151-156.
41. Bruns, J., Jr. and Hauser, W. A. (2003) The epidemiology of traumatic brain injury: a review. Epilepsia 44(Suppl 10), 2-10.
42. Werner, C. and Engelhard, K. (2007) Pathophysiology of traumatic brain injury. Br. J. Anaesth 99, 4-9.
43. Raghupathi, R. (2004) Cell death mechanisms following traumatic brain injury. Brain Pathol. 14, 215-222.
44. Skoglosa, Y., Lewen, A., Takei, N., Hillered, L. and Lindholm, D. (1999) Regulation of pituitary adenylate cyclase activating polypeptide and its receptor type 1 after traumatic brain injury: comparison with brain-derived neurotrophic factor and the induction of neuronal cell death. Neuroscience 90, 235-247.
45. Tamas, A., Reglodi, D., Farkas, O., Kovesdi, E., Pal, J., Povlishock, J.T., Schwarcz, A., Czeiter, E., Szanto, Z., Doczi, T., Buki, A. and Bukovics, P. (2012) Effect of PACAP in central and peripheral nerve injuries. Int. J. Mol. Sci. 13, 8430-8448.
46. Kovesdi, E., Tamas, A., Reglodi, D., Farkas, O., Pal, J., Toth, G., Bukovics, P., Doczi, T. and Buki, A. (2008) Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats. Neurotox. Res. 13, 71-78.
47. Johanson, C., Stopa, E., Baird, A. and Sharma, H. (2011) Traumatic brain injury and recovery mechanisms: peptide modulation of periventricular neurogenic regions by the choroid plexus-CSF nexus. J. Neural. Transm. 118, 115-133.
48. Mao, S. S., Hua, R., Zhao, X. P., Qin, X., Sun, Z. Q., Zhang, Y., Wu, Y. Q., Jia, M. X., Cao, J. L. and Zhang, Y. M. (2012) Exogenous administration of PACAP alleviates traumatic brain injury in rats through a mechanism involving the TLR4/MyD88/NF-?B pathway. J. Neurotrauma 29, 1941-1959.
49. Ziebell, J. M. and Morganti-Kossmann, M. C. (2010) Involvement of Pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics. 7, 22-30.
50. Marklund, N., Bakshi, A., Castelbuono, D. J., Conte, V. and McIntosh, T. K. (2006) Evaluation of pharmacological treatment strategies in traumatic brain injury. Curr. Pharm. Des. 12, 1645-1680.
51. Fang, K. M., Chen, J. K., Hung, S. C., Chen, M. C., Wu, Y. T., Wu, T. J., Lin, H. I., Chen, C. H., Cheng, H., Yang, C. S. and Tzeng, S. F. (2010) Effects of combinatorial treatment with pituitary adenylate cyclase activating peptide and human mesenchymal stem cells on spinal cord tissue repair. PLoS One 5, e15299.
52. Kim, D. H., Ko, I. G., Kim, B. K., Kim, T. W., Kim, S. E., Shin, M. S., Kim, C. J., Kim, H., Kim, K. M. and Baek, S. S. (2010) Treadmill exercise inhibits traumatic brain injury-induced hippocampal apoptosis. Physiol. Behav. 101, 660-665.
53. Reglodi, D., Kiss, P., Lubics, A. and Tamas, A. (2011) Review on the protective effects of PACAP in models of neurodegenerative diseases In Vitro and In Vivo. Curr. Pharm. Des. 17, 962-972.
54. Leker, R. R. and Shohami, E. (2002) Cerebral ischemia and trauma-different etiologies yet similar mechanisms: neuroprotective opportunities. Brain Res. Brain Res. Rev. 39, 55-73.
55. Buki, A., Okonkwo, D. O., Wang, K. K. and Povlishock, J. T. (2000) Cytochrome c release and caspase activation in traumatic axonal injury. J. Neurosci. 20, 2825-2834.
56. Jankovic, J. (2008) Parkinson's disease: Clinical features and diagnosis. J. Neurol. Neurosurg. Psychiatry 79, 368-376.
57. Gerlach, M. and Riederer, P. (1996) Animal models of Parkinson's disease: an empirical comparison with the phenomenology of the disease in man. J. Neural. Transm. 103, 987-1041.
58. Kostrzewa, R. M. and Segura-Aguilar, J. (2002) Neurotoxicological and neuroprotective elements in Parkinson's disease. Neurotox. Res. 4, 83-86.
59. Masuo, Y., Matsumoto, Y., Tokito, F., Tsuda, M. and Fujino, M. (1993) Effects of vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) on the spontaneous release of acetylcholine from the rat hippocampus by brain microdialysis. Brain Res. 611, 207-215.
60. Deumens, R., Blokland, A. and Prickaerts, J. (2002) Modeling Parkinson's disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp. Neurol. 175, 303-317.
61. Reglodi, D., Lubics, A., Tamas, A., Szalontay, L. and Lengvari, I. (2004) Pituitary adenylate cyclase activating polypeptide protects dopaminergic neurons and improves behavioral deficits in a rat model of Parkinson's disease. Behav. Brain Res. 151, 303-312.
62. Reglodi, D., Tamas, A., Lubics, A., Szalontay, L. and Lengvari, I. (2004) Morphological and functional effects of PACAP in 6-hydroxydopamine-induced lesion of the substantia nigra in rats. Regul. Pept. 123, 85-94.
63. Wang, G., Qi, C., Fan, G. H., Zhou, H. Y. and Chen, S. D. (2005) PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone. FEBS Lett. 579, 4005-4011.
64. Takei, N., Skoglösa, Y. and Lindholm, D. (1998) Neurotrophic and neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on mesencephalic dopaminergic neurons. J. Neurosci. Res. 54, 698-706.
65. Chung, C. Y., Seo, H., Sonntag, K. C., Brooks, A., Lin, L. and Isacson, O. (2005) Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection. Hum. Mol. Genet. 14, 1709-1725.
66. Brown, D., Tamas, A., Reglodi, D. and Tizabi, Y. (2013) PACAP protects against salsolinol-induced toxicity in dop aminergic SH-SY5Y cells: implication for Parkinson's disease. J. Mol. Neurosci. 50, 600-607.
67. von Bohlen und Halbach, O., Schober, A. and Krieglstein, K. (2004) Genes, proteins, and neurotoxins involved in Parkinson's disease. Prog. Neurobiol. 73, 151-177.
68. Yang, S., Yang, J., Yang, Z., Chen, P., Fraser, A., Zhang, W., Pang, H., Gao, X., Wilson, B., Hong, J. S. and Block, M. L. (2006) Pituitary adenylate cyclase-activating polypeptide (PACAP) 38 and PACAP4-6 are neuroprotective through inhibition of NADPH oxidase: potent regulators of microglia-mediated oxidative stress. J. Pharmacol. Exp. Ther. 319, 595-603.
69. Przywara, D. A., Guo, X., Angelilli, M. L., Wakade, T. D. and Wakade, A. R. (1996) A non-cholinergic transmitter, pituitary adenylate cyclase-activating polypeptide, utilizes a novel mechanism to evoke catecholamine secretion in rat adrenal chromaffin cells. J. Biol. Chem. 271, 10545-10550.
70. Ghzili, H., Grumolato, L., Thouennon, E., Tanguy, Y., Turquier, V., Vaudry, H. and Anouar, Y. (2008) Role of PACAP in the physiology and pathology of the sympathoadrenal system. Front Neuroendocrinol. 29, 128-141.
71. Mustafa, T., Walsh, J., Grimaldi, M. and Eiden, L. E. (2010) PAC1hop receptor activation facilitates catecholamine secretion selectively through 2-APB-sensitive Ca(2+) channels in PC12 cells. Cell Signal. 22, 1420-1426.
72. Wang, G., Pan, J., Tan, Y. Y., Sun, X. K., Zhang, Y. F., Zhou, H. Y., Ren, R. J., Wang, X. J. and Chen, S. D. (2008) Neuroprotective effects of PACAP27 in mice model of Parkinson's disease involved in the modulation of K(ATP) subunits and D2 receptors in the striatum. Neuropeptides 42, 267-276.
73. Deguil, J., Jailloux, D., Page, G., Fauconneau, B., Houeto, J. L., Philippe, M., Muller, J. M. and Pain, S. (2007) Neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in MPP+-induced alteration of translational control in Neuro-2a neuroblastoma cells. J. Neurosci. Res. 85, 2017-2025.
74. Deguil, J., Chavant, F., Lafay-Chebassier, C., Perault-Pochat, M. C., Fauconneau, B. and Pain, S. (2010) Neuroprotective effect of PACAP on translational control alteration and cognitive decline in MPTP parkinsonian mice. Neurotox. Res. 17, 142-155.
75. Hardy, J. and Selkoe, D. J. (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356.
76. LaFerla, F. M., Green, K. N. and Oddo, S. (2007) Intracellular amyloid-beta in Alzheimer's disease. Nat. Rev. Neurosci. 8, 499-509.
77. Kojro, E., Postina, R., Buro, C., Meiringer, C., Gehrig-Burger, K. and Fahrenholz, F. (2006) The neuropeptide PACAP promotes the 〈 -secretase pathway for processing the Alzheimer amyloid precursor protein. FASEB J. 20, 512-514.
78. Rat, D., Schmitt, U., Tippmann, F., Dewachter, I., Theunis, C., Wieczerzak, E., Postina, R., Van Leuven, F., Fahrenholz, F. and Kojro, E. (2011) Neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) slows down Alzheimer's disease-like pathology in amyloid precursor protein-transgenic mice. FASEB J. 25, 3208-3218.
79. Wu, Z. L., Ciallella, J. R., Flood, D. G., O'Kane, T. M., Bozyczko-Coyne, D. and Savage, M. J. (2006) Comparative analysis of cortical gene expression in mouse models of Alzheimer's disease. Neurobiol. Aging 27, 377-386.
80. Dogrukol-Ak, D., Kumar, V. B., Ryerse, J. S., Farr, S. A., Verma, S., Nonaka, N., Nakamachi, T., Ohtaki, H., Niehoff, M. L., Edwards, J. C., Shioda, S., Morley, J. E. and Banks, W. A. (2009) Isolation of peptide transport system-6 from brain endothelial cells: therapeutic effects with antisense inhibition in Alzheimer and stroke models. J. Cereb. Blood Flow Metab. 29, 411-422.
81. Strittmatter, W. J. and Roses, A. D. (1995) Apolipoprotein E and Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 92, 4725-4727.
82. Plump, A. S., Smith, J. D., Hayek, T., Aalto-Setala, K., Walsh, A., Verstuyft, J. G., Rubin, E. M. and Breslow, J. L. (1992) Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71, 343-353.
83. Gozes, I., Bachar, M., Bardea, A., Davidson, A., Rubinraut, S., Fridkin, M. and Giladi, E. (1997) Protection against developmental retardation in apolipoprotein E-deficient mice by a fatty neuropeptide: implications for early treatment of Alzheimer's disease. J. Neurobiol. 33, 329-342.
84. Onoue, S., Endo, K., Ohshima, K., Yajima, T. and Kashimoto, K. (2002) The neuropeptide PACAP attenuates beta-amyloid (1-42)-induced toxicity in PC12 cells. Peptides 23, 1471-1478.
85. Zhu, L., Tamvakopoulos, C., Xie, D., Dragovic, J., Shen, X., Fenyk-Melody, J. E., Schmidt, K., Bagchi, A., Griffin, P. R., Thornberry, N. A. and Sinha Roy, R. (2003) The role of dipeptidyl peptidase IV in the cleavage of glucagon family peptides: in vivo metabolism of pituitary adenylate cyclase activating polypeptide-(1-38). J. Biol. Chem. 278, 22418-22423.
86. Bourgault, S., Vaudry, D., Botia, B., Couvineau, A., Laburthe, M., Vaudry, H. and Fournier, A. (2008) Novel stable PACAP analogs with potent activity towards the PAC1 receptor. Peptides 29, 919-932.
87. Bourgault, S., Vaudry, D., Dejda, A., Doan, N. D., Vaudry, H. and Fournier, A. (2009) Pituitary adenylate cyclase-activating polypeptide: focus on structure-activity relationships of a neuroprotective Peptide. Curr. Med. Chem. 16, 4462-4480.