{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:25:40Z","timestamp":1791199540031,"version":"4.2.0"},"reference-count":86,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,12]],"date-time":"2006-01-12T00:00:00Z","timestamp":1137024000000},"content-version":"vor","delay-in-days":407,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2004,12]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson\u2010dementia complex of Guam, all of the tauopathies, and age\u2010related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two\u2010edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte\u2010directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue\u2010based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti\u2010inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti\u2010inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken of opportunities indicated by these epidemiological studies to treat AD and PD with appropriate anti\u2010inflammatory agents. Based on this evidence, classical NSAIDs are the most logical choice. Dosage, though, must be sufficient to combat the inflammation. Analysis of mRNA levels of inflammatory mediators indicates that the intensity of inflammation is considerably higher in AD hippocampus and in PD substantia nigra than in osteoarthritic joints. Thus, full therapeutic doses of NSAIDs, or combinations of anti\u2010inflammatory agents, are needed to achieve the suggested neurological benefits.<\/jats:p>","DOI":"10.1196\/annals.1332.007","type":"journal-article","created":{"date-parts":[[2005,1,29]],"date-time":"2005-01-29T01:15:36Z","timestamp":1106961336000},"page":"104-116","source":"Crossref","is-referenced-by-count":435,"title":["Inflammation and the Degenerative Diseases of Aging"],"prefix":"10.1111","volume":"1035","author":[{"given":"PATRICK L.","family":"McGEER","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EDITH G.","family":"McGEER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,12]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)00124-X"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(03)00124-6"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2004.01.005"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002826-200301000-00005"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.10191"},{"key":"e_1_2_9_7_2","unstructured":"Haymaker W.&R.D.Adams Eds.1982.Histology and Histopathology of the Nervous System pp. 1150\u20131173. Charles C. Thomas. Springfield IL."},{"key":"e_1_2_9_8_2","unstructured":"Metchnikoff E. 1892. Lecons sur la pathologie comparee de l'inflammation. Masson. Paris."},{"key":"e_1_2_9_9_2","first-page":"154","article-title":"El \u2018tercer elemento\u2019 de los centros nerviosos. Poder fagocitario y movilidad de la microglia","volume":"9","author":"Hortega P.","year":"1919","journal-title":"Bol. Soc. Esp. Biol. Ano."},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0171-2985(82)80072-7"},{"key":"e_1_2_9_11_2","unstructured":"Davis R.L. & D.M. Robertson Eds. 1991. Textbook of Neuropathology. Second edition pp. 141\u2013163. Williams & Wilkins. Baltimore."},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0173(95)00011-9"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(88)90263-7"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00689592"},{"key":"e_1_2_9_15_2","first-page":"77","article-title":"Microglia and the process of phagocytosis in gliomas","volume":"1","author":"Penfield W.","year":"1925","journal-title":"Am. J. Pathol."},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199910)46:4<598::AID-ANA7>3.0.CO;2-F"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10728"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/hq0701.092160"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.83.8.860"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0602325"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2004.03.016"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(87)80305-8"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(94)90067-1"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0047-6374(01)00249-4"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/niox.2001.0399"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.440070117"},{"key":"e_1_2_9_27_2","doi-asserted-by":"crossref","first-page":"6021","DOI":"10.1523\/JNEUROSCI.16-19-06021.1996","article-title":"Specific domains of \u03b2\u2010amyloid from Alzheimer plaque elicit neuronal killing in human microglia","volume":"16","author":"Giulian D.","year":"1996","journal-title":"J. Neurosci."},{"key":"e_1_2_9_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.1.127"},{"key":"e_1_2_9_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(97)00094-5"},{"key":"e_1_2_9_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00289-5"},{"key":"e_1_2_9_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(97)00042-0"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.21.10016"},{"key":"e_1_2_9_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(01)00288-3"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1385-299X(01)00119-2"},{"key":"e_1_2_9_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0162-3109(00)00205-8"},{"key":"e_1_2_9_36_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3089.1999.00007.x"},{"key":"e_1_2_9_37_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1999.5704"},{"key":"e_1_2_9_38_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199907000-00024"},{"key":"e_1_2_9_39_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.175.5.1373"},{"key":"e_1_2_9_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.11.3689"},{"key":"e_1_2_9_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(90)90941-4"},{"key":"e_1_2_9_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02970-X"},{"key":"e_1_2_9_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)91148-T"},{"key":"e_1_2_9_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/1243"},{"key":"e_1_2_9_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20001204)96:6<823::AID-AJMG26>3.0.CO;2-I"},{"key":"e_1_2_9_46_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.4.480"},{"key":"e_1_2_9_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200003)47:3<361::AID-ANA12>3.0.CO;2-N"},{"key":"e_1_2_9_48_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1996.4601"},{"key":"e_1_2_9_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(00)82845-6"},{"key":"e_1_2_9_50_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200009)48:3<388::AID-ANA16>3.0.CO;2-G"},{"key":"e_1_2_9_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)04008-3"},{"key":"e_1_2_9_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200003)47:3<365::AID-ANA13>3.0.CO;2-G"},{"key":"e_1_2_9_53_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199905)45:5<666::AID-ANA18>3.0.CO;2-3"},{"key":"e_1_2_9_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(00)01487-7"},{"key":"e_1_2_9_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10196"},{"key":"e_1_2_9_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00301-4"},{"key":"e_1_2_9_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(02)00300-2"},{"key":"e_1_2_9_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.5.1977"},{"key":"e_1_2_9_59_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.58.11.1790"},{"key":"e_1_2_9_60_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2.7.1137"},{"key":"e_1_2_9_61_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.1.5.1041"},{"key":"e_1_2_9_62_2","first-page":"188","article-title":"Infliximab for the treatment of Crohn's disease: efficacy, safety and pharmacoeconomics","volume":"8","author":"Feagan B.G.","year":"2001","journal-title":"Can. J. Clin. Pharmacol."},{"key":"e_1_2_9_63_2","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1523\/JNEUROSCI.20-15-j0004.2000","article-title":"Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage","volume":"20","author":"Chapman G.A.","year":"2000","journal-title":"J. Neurosci."},{"key":"e_1_2_9_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1136(20000215)29:4<305::AID-GLIA2>3.0.CO;2-V"},{"key":"e_1_2_9_65_2","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.57.11.1586"},{"key":"e_1_2_9_66_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.2.425"},{"key":"e_1_2_9_67_2","doi-asserted-by":"publisher","DOI":"10.1159\/000078501"},{"key":"e_1_2_9_68_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.48.3.626"},{"key":"e_1_2_9_69_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010178"},{"key":"e_1_2_9_70_2","doi-asserted-by":"publisher","DOI":"10.1159\/000048621"},{"key":"e_1_2_9_71_2","first-page":"S143","article-title":"Nonsteroidal antiinflammatory drugs and the risk of Parkinson's disease","volume":"17","author":"Chen H.","year":"2002","journal-title":"Movement Dis."},{"key":"e_1_2_9_72_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.54.3.588"},{"key":"e_1_2_9_73_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.7.1050"},{"key":"e_1_2_9_74_2","unstructured":"Sainali S.M.et al.2000. Results of a double\u2010blind placebo\u2010controlled study of celecoxib for the progression of Alzheimer's disease.InSixth International Stockholm\u2010Springfield Symposium of Advances in Alzheimer Therapy p. 180."},{"key":"e_1_2_9_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)05623-9"},{"key":"e_1_2_9_76_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03035134"},{"key":"e_1_2_9_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01389-X"},{"key":"e_1_2_9_78_2","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-200017010-00001"},{"key":"e_1_2_9_79_2","first-page":"2927","article-title":"Hydroxychloroquine neuromyotoxicity","volume":"27","author":"Stein M.","year":"2000","journal-title":"J. Rheumatol."},{"key":"e_1_2_9_80_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.43.8.1609"},{"key":"e_1_2_9_81_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.53.1.197"},{"key":"e_1_2_9_82_2","doi-asserted-by":"publisher","DOI":"10.3143\/geriatrics.37.212"},{"key":"e_1_2_9_83_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00014-3"},{"key":"e_1_2_9_84_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.21.2819"},{"key":"e_1_2_9_85_2","first-page":"10","article-title":"Disease modifying antirheumatic drugs: longterm safety issues","volume":"62","author":"Capell H.A.","year":"2001","journal-title":"J. Rheumatol. (Suppl.)"},{"key":"e_1_2_9_86_2","first-page":"121","article-title":"Nitric oxide\u2010releasing NSAIDs: a novel class of GI\u2010sparing anti\u2010inflammatory drugs","volume":"46","author":"Wallace J.L.","year":"1995","journal-title":"Agents Actions (Suppl.)"},{"key":"e_1_2_9_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(99)01514-0"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1332.007","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1332.007","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T20:02:56Z","timestamp":1695672176000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1332.007"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12]]},"references-count":86,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,12]]}},"alternative-id":["10.1196\/annals.1332.007"],"URL":"https:\/\/doi.org\/10.1196\/annals.1332.007","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12]]}}}