{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:25:06Z","timestamp":1792016706263,"version":"4.4.0"},"reference-count":63,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T00:00:00Z","timestamp":1209340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) is characterized by extracellular deposits of fibrillar \u03b2\u2010amyloid (A\u03b2) in the brain, increased microglial\u2010mediated inflammatory reactions in senile plaques, selective neuronal death, and cognitive deficits. The use of agents that limit microglial activation and inflammation in AD has recently emerged as an attractive therapeutic strategy for this disease. The vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, has shown neuroprotective effects in acute brain damage<jats:italic>in vivo<\/jats:italic>and potent anti\u2010inflammatory actions in central nervous system. Here, we report that VIP inhibits A\u03b2\u2010induced neurodegeneration by indirectly inhibiting the production of a wide panel of inflammatory and neurotoxic agents by activated microglia cells. The inhibitory effect of VIP is mediated by blocking signaling through the p38 MAPK, p42\/p44 MAPK, and NFkB cascades, the three major transduction pathways involved in the transcription of inflammatory mediators and the production of free radicals by A\u03b2\u2010activated microglia cells. Based on its neuroprotective action and its efficacy in inhibiting a broad range of inflammatory responses, VIP may provide a novel therapeutic approach to AD. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/glia.20681","type":"journal-article","created":{"date-parts":[[2008,4,28]],"date-time":"2008-04-28T21:17:04Z","timestamp":1209417424000},"page":"1091-1103","source":"Crossref","is-referenced-by-count":75,"title":["Vasoactive intestinal peptide protects against \u03b2\u2010amyloid\u2010induced neurodegeneration by inhibiting microglia activation at multiple levels"],"prefix":"10.1002","volume":"56","author":[{"given":"Mario","family":"Delgado","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nieves","family":"Varela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Gonzalez\u2010Rey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,4,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(84)90353-7"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.649"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/78682"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2007.04.002"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.8.2736"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-02-00558.2000"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.2.720"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn941"},{"key":"e_1_2_5_10_1","first-page":"307","article-title":"Neuroprotective potential of three neuropeptides PACAP, VIP and PHI","volume":"57","author":"Dejda A","year":"2005","journal-title":"Pharmacol Rep"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02305-7"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303199200"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006923200"},{"key":"e_1_2_5_14_1","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1096\/fj.02-1029fje","article-title":"Vasoactive intestinal peptide prevents activated microglia\u2010induced neurodegeneration under inflammatory conditions: potential therapeutic role in brain trauma","volume":"17","author":"Delgado M","year":"2003","journal-title":"FASEB J"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0799fje"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10098"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0702372"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.56.2.7"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.7839144"},{"key":"e_1_2_5_20_1","first-page":"86","article-title":"Alzheimer's disease. A double\u2010labeling immunohistochemical study of senile plaques","volume":"132","author":"Dickson DW","year":"1988","journal-title":"Am J Pathol"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440070113"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(79)91109-0"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2490-06.2006"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2002.0538"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90562-N"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1984"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2007.07.001"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.22.1.219"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(97)00230-1"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(97)00228-3"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.1.427"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02782501"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1159\/000124886"},{"key":"e_1_2_5_34_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/S0031-6997(24)01360-7","article-title":"International Union of Pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase\u2010activating polypeptide","volume":"50","author":"Harmar AJ","year":"1998","journal-title":"Pharmacol Rev"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00142.2005"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/00062752-199901000-00004"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-16-06309.2000"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(87)90041-0"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.10151"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/370223a0"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.4.986"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-12-04451.1998"},{"key":"e_1_2_5_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-07-02284.1997"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0531-5565(98)00013-8"},{"key":"e_1_2_5_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90696-3"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440070114"},{"key":"e_1_2_5_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.65.4.409"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.2.447"},{"key":"e_1_2_5_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/374647a0"},{"key":"e_1_2_5_50_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.308.5723.778"},{"key":"e_1_2_5_51_1","first-page":"966","article-title":"Maxadilan, the vasodilator from sand flies, is a specific pituitary adenylate cyclase activating peptide type I receptor agonist","volume":"271","author":"Moro O","year":"1996","journal-title":"J Biol Chem"},{"key":"e_1_2_5_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(02)00085-2"},{"key":"e_1_2_5_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209478200"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4652-05.2006"},{"key":"e_1_2_5_55_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.45.1.51"},{"key":"e_1_2_5_56_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1609"},{"key":"e_1_2_5_57_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M308372200"},{"key":"e_1_2_5_58_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.3.626"},{"key":"e_1_2_5_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.07.009"},{"key":"e_1_2_5_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-06-02161.1998"},{"key":"e_1_2_5_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/87945"},{"key":"e_1_2_5_62_1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0022-3565(24)36654-6","article-title":"Novel cyclic peptide agonist of high potency and selectivity for the type II vasoactive intestinal peptide receptor","volume":"281","author":"Xia M","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_5_63_1","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1523\/JNEUROSCI.22-09-03484.2002","article-title":"Peroxynitrite mediates neurotoxicity of amyloid \u03b2\u2010peptide1\u201042\u2010 and lipopolysaccharide\u2010activated microglia","volume":"22","author":"Xie Z","year":"2002","journal-title":"J Neurosci"},{"key":"e_1_2_5_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(95)00043-E"}],"container-title":["Glia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fglia.20681","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/glia.20681","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T22:57:10Z","timestamp":1738191430000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/glia.20681"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4,28]]},"references-count":63,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["10.1002\/glia.20681"],"URL":"https:\/\/doi.org\/10.1002\/glia.20681","archive":["Portico"],"relation":{},"ISSN":["0894-1491","1098-1136"],"issn-type":[{"value":"0894-1491","type":"print"},{"value":"1098-1136","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,28]]}}}