{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T14:16:24Z","timestamp":1791209784678,"version":"4.1.0"},"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2008,8,6]],"date-time":"2008-08-06T00:00:00Z","timestamp":1217980800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0002906","type":"journal-article","created":{"date-parts":[[2008,8,5]],"date-time":"2008-08-05T17:41:11Z","timestamp":1217958071000},"page":"e2906","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":136,"title":["Disruption of Neuronal Autophagy by Infected Microglia Results in Neurodegeneration"],"prefix":"10.1371","volume":"3","author":[{"given":"Mehrdad","family":"Alirezaei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Kiosses","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia T.","family":"Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan R.","family":"Brady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard S.","family":"Fox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2008,8,6]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/sj.cdd.4402120","article-title":"Constitutive autophagy: vital role in clearance of unfavorable proteins in neurons.","volume":"14","author":"M Komatsu","year":"2007","journal-title":"Cell Death Differ"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1534-5807(04)00099-1","article-title":"Development by self-digestion: molecular mechanisms and biological functions of autophagy.","volume":"6","author":"B Levine","year":"2004","journal-title":"Dev Cell"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.mam.2006.08.009","article-title":"Neuronal macroautophagy: from development to degeneration.","volume":"27","author":"B Boland","year":"2006","journal-title":"Mol Aspects Med"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1016\/j.biocel.2004.05.008","article-title":"Involvement of macroautophagy in the dissolution of neuronal inclusions.","volume":"36","author":"HJ Rideout","year":"2004","journal-title":"Int J Biochem Cell Biol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nrd2272","article-title":"Potential therapeutic applications of autophagy.","volume":"6","author":"DC Rubinsztein","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/35056522","article-title":"Molecular dissection of autophagy: two ubiquitin-like systems.","volume":"2","author":"Y Ohsumi","year":"2001","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"33889","DOI":"10.1074\/jbc.273.51.33889","article-title":"A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy.","volume":"273","author":"N Mizushima","year":"1998","journal-title":"J Biol Chem"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1083\/jcb.152.4.657","article-title":"Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells.","volume":"152","author":"N Mizushima","year":"2001","journal-title":"J Cell Biol"},{"key":"ref9","article-title":"The ATG12-ATG5 conjugate has a novel e3-like activity for protein lipidation in autophagy.","author":"T Hanada","year":"2007","journal-title":"J Biol Chem"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"5720","DOI":"10.1093\/emboj\/19.21.5720","article-title":"LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.","volume":"19","author":"Y Kabeya","year":"2000","journal-title":"Embo J"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nature04724","article-title":"Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.","volume":"441","author":"T Hara","year":"2006","journal-title":"Nature"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nature04723","article-title":"Loss of autophagy in the central nervous system causes neurodegeneration in mice.","volume":"441","author":"M Komatsu","year":"2006","journal-title":"Nature"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"16023","DOI":"10.1074\/jbc.275.21.16023","article-title":"Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages.","volume":"275","author":"T Ishii","year":"2000","journal-title":"J Biol Chem"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1006\/bbrc.2000.4107","article-title":"Ubiquitin-binding protein p62 expression is induced during apoptosis and proteasomal inhibition in neuronal cells.","volume":"280","author":"E Kuusisto","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1038\/sj.onc.1206325","article-title":"p62 overexpression in breast tumors and regulation by prostate-derived Ets factor in breast cancer cells.","volume":"22","author":"HG Thompson","year":"2003","journal-title":"Oncogene"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1083\/jcb.200507002","article-title":"p62\/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death.","volume":"171","author":"G Bjorkoy","year":"2005","journal-title":"J Cell Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"p62\/SQSTM1 binds directly to Atg8\/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.","volume":"282","author":"S Pankiv","year":"2007","journal-title":"J Biol Chem"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.cell.2007.10.035","article-title":"Homeostatic Levels of p62 Control Cytoplasmic Inclusion Body Formation in Autophagy-Deficient Mice.","volume":"131","author":"M Komatsu","year":"2007","journal-title":"Cell"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"8057","DOI":"10.1523\/JNEUROSCI.2261-06.2006","article-title":"Induction of autophagy in axonal dystrophy and degeneration.","volume":"26","author":"QJ Wang","year":"2006","journal-title":"J Neurosci"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1097\/00126334-200210012-00004","article-title":"HIV-1-associated dementia: a metabolic encephalopathy perpetrated by virus-infected and immune-competent mononuclear phagocytes.","volume":"31","author":"E Anderson","year":"2002","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/nri1527","article-title":"The neuropathogenesis of AIDS.","volume":"5","author":"F Gonzalez-Scarano","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1038\/nn1988","article-title":"Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease.","volume":"10","author":"CS Lobsiger","year":"2007","journal-title":"Nat Neurosci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/BF00294450","article-title":"Prominent cortical atrophy with neuronal loss as correlate of human immunodeficiency virus encephalopathy.","volume":"82","author":"F Gray","year":"1991","journal-title":"Acta Neuropathol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/ana.410320304","article-title":"Spectrum of human immunodeficiency virus-associated neocortical damage.","volume":"32","author":"E Masliah","year":"1992","journal-title":"Ann Neurol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1002\/ana.410420618","article-title":"Dendritic injury is a pathological substrate for human immunodeficiency virus-related cognitive disorders. HNRC Group. The HIV Neurobehavioral Research Center.","volume":"42","author":"E Masliah","year":"1997","journal-title":"Ann Neurol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/sj.cdd.4401577","article-title":"Cell death in HIV dementia.","volume":"12","author":"MP Mattson","year":"2005","journal-title":"Cell Death Differ"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1080\/13550280490279816","article-title":"Brain aging in acquired immunodeficiency syndrome: increased ubiquitin-protein conjugate is correlated with decreased synaptic protein but not amyloid plaque accumulation.","volume":"10","author":"BB Gelman","year":"2004","journal-title":"J Neurovirol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1523\/JNEUROSCI.4617-05.2006","article-title":"Human immunodeficiency virus (HIV)-induced neurotoxicity: roles for the NMDA receptor subtypes.","volume":"26","author":"LA O'Donnell","year":"2006","journal-title":"J Neurosci"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1111\/j.1471-4159.2007.04746.x","article-title":"Activation of cyclin-dependent kinase 5 by calpains contributes to human immunodeficiency virus-induced neurotoxicity.","volume":"103","author":"Y Wang","year":"2007","journal-title":"J Neurochem"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrm1660","article-title":"Autophagy in metazoans: cell survival in the land of plenty.","volume":"6","author":"JJ Lum","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1091\/mbc.E03-09-0704","article-title":"In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker.","volume":"15","author":"N Mizushima","year":"2004","journal-title":"Mol Biol Cell"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"323","DOI":"10.4161\/auto.4012","article-title":"LC3, an autophagosome marker, can be incorporated into protein aggregates independent of autophagy: caution in the interpretation of LC3 localization.","volume":"3","author":"A Kuma","year":"2007","journal-title":"Autophagy"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1247\/csf.27.421","article-title":"Autophagosome formation in mammalian cells.","volume":"27","author":"N Mizushima","year":"2002","journal-title":"Cell Struct Funct"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"542","DOI":"10.4161\/auto.4600","article-title":"How to Interpret LC3 Immunoblotting.","volume":"3","author":"N Mizushima","year":"2007","journal-title":"Autophagy"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1006\/bbrc.1997.6221","article-title":"Low micromolar levels of hydrogen peroxide and proteasome inhibitors induce the 60-kDa A170 stress protein in murine peritoneal macrophages.","volume":"232","author":"T Ishii","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4161\/auto.5338","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes.","volume":"4","author":"DJ Klionsky","year":"2008","journal-title":"Autophagy"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrm2239","article-title":"Self-eating and self-killing: crosstalk between autophagy and apoptosis.","volume":"8","author":"MC Maiuri","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cub.2006.10.053","article-title":"Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death.","volume":"17","author":"RC Scott","year":"2007","journal-title":"Curr Biol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1128\/MCB.25.3.1025-1040.2005","article-title":"Inhibition of macroautophagy triggers apoptosis.","volume":"25","author":"P Boya","year":"2005","journal-title":"Mol Cell Biol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/sj.cdd.4401623","article-title":"HIV-1 infection and AIDS: consequences for the central nervous system.","volume":"12","author":"M Kaul","year":"2005","journal-title":"Cell Death Differ"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"5641","DOI":"10.1074\/jbc.M609532200","article-title":"Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein.","volume":"282","author":"S Sarkar","year":"2007","journal-title":"J Biol Chem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nchembio883","article-title":"Small molecules enhance autophagy and reduce toxicity in Huntington's disease models.","volume":"3","author":"S Sarkar","year":"2007","journal-title":"Nat Chem Biol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1083\/jcb.200510065","article-title":"Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway.","volume":"172","author":"A Yamamoto","year":"2006","journal-title":"J Cell Biol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/sj.cdd.4401936","article-title":"Response to myocardial ischemia\/reperfusion injury involves Bnip3 and autophagy.","volume":"14","author":"A Hamacher-Brady","year":"2007","journal-title":"Cell Death Differ"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/sj.cdd.4402030","article-title":"DNA damaging agent-induced autophagy produces a cytoprotective adenosine triphosphate surge in malignant glioma cells.","volume":"14","author":"M Katayama","year":"2007","journal-title":"Cell Death Differ"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"34568","DOI":"10.1074\/jbc.M303221200","article-title":"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins.","volume":"278","author":"T Lamark","year":"2003","journal-title":"J Biol Chem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1471-4159.2004.02692.x","article-title":"Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions.","volume":"91","author":"U Nagaoka","year":"2004","journal-title":"J Neurochem"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0002-9440(10)64369-6","article-title":"p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases.","volume":"160","author":"K Zatloukal","year":"2002","journal-title":"Am J Pathol"},{"key":"ref49","first-page":"4","article-title":"Lysine 63-linked polyubiquitin potentially partners with p62 to promote the clearance of protein inclusions by autophagy.","author":"JM Tan","year":"2007","journal-title":"Autophagy"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"11047","DOI":"10.1523\/JNEUROSCI.2733-07.2007","article-title":"Human immunodeficiency virus-1\/surface glycoprotein 120 induces apoptosis through RNA-activated protein kinase signaling in neurons.","volume":"27","author":"M Alirezaei","year":"2007","journal-title":"J Neurosci"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1002\/jnr.490420510","article-title":"Serum-free B27\/neurobasal medium supports differentiated growth of neurons from the striatum, substantia nigra, septum, cerebral cortex, cerebellum, and dentate gyrus.","volume":"42","author":"GJ Brewer","year":"1995","journal-title":"J Neurosci Res"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1006\/viro.1995.1503","article-title":"Serial passage of microglial SIV results in selection of homogeneous env quasispecies in the brain.","volume":"212","author":"TE Lane","year":"1995","journal-title":"Virology"},{"key":"ref53","first-page":"914","article-title":"Transfer of neuropathogenic simian immunodeficiency virus with naturally infected microglia.","volume":"146","author":"D Watry","year":"1995","journal-title":"Am J Pathol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"5429","DOI":"10.4049\/jimmunol.167.9.5429","article-title":"Highly activated CD8(+) T cells in the brain correlate with early central nervous system dysfunction in simian immunodeficiency virus infection.","volume":"167","author":"MC Marcondes","year":"2001","journal-title":"J Immunol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"5812","DOI":"10.4049\/jimmunol.178.9.5812","article-title":"Enrichment and persistence of virus-specific CTL in the brain of simian immunodeficiency virus-infected monkeys is associated with a unique cytokine environment.","volume":"178","author":"MC Marcondes","year":"2007","journal-title":"J Immunol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0002906","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,13]],"date-time":"2019-05-13T00:17:49Z","timestamp":1557706669000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0002906"}},"subtitle":[],"editor":[{"given":"Xiao-Jiang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2008,8,6]]},"references-count":55,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2008,8,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0002906","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,8,6]]}}}