{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:57:51Z","timestamp":1793840271321,"version":"4.6.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T00:00:00Z","timestamp":1726012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Dementia is an umbrella term used to describe deterioration of cognitive function. It is the seventh leading cause of death and is one of the major causes of dependence among older people globally. Alzheimer\u2019s Disease (AD) contributes to approximately 60\u201370% of dementia cases and is characterized by the accumulation of amyloid plaques and tau tangles in the brain. Neuroinflammation is now widely accepted as another disease hallmark, playing a role in both the response to and the perpetuation of disease processes. Microglia are brain-resident immune cells that are initially effective at clearing amyloid plaques but contribute to the damaging inflammatory milieu of the brain as disease progresses. Circulating peripheral immune cells contribute to this inflammatory environment through cytokine secretion, creating a positive feedback loop with the microglia. One group of these peripherally derived cytokines acting on microglia is the common cytokine receptor \u03b3 chain family. These cytokines bind heterodimer receptors to activate three major signaling pathways: MAPK, PI3K, and JAK\/STAT. This perspective will look at the mechanisms of these three pathways in microglia and highlight the future directions of this research and potential therapeutics.<\/jats:p>","DOI":"10.3389\/fnmol.2024.1441691","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T05:11:30Z","timestamp":1726031490000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Common cytokine receptor gamma chain family cytokines activate MAPK, PI3K, and JAK\/STAT pathways in microglia to influence Alzheimer\u2019s Disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Hannah","family":"Zuppe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s00018-022-04347-6","article-title":"Impact of IL-21-associated peripheral and brain crosstalk on the Alzheimer\u2019s Disease neuropathology","volume":"79","author":"Agrawal","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"273","DOI":"10.14283\/jpad.2017.41","article-title":"Neflamapimod: clinical phase 2b-ready Oral small molecule inhibitor of P38\u03b1 to reverse synaptic dysfunction in early Alzheimer\u2019s Disease","volume":"4","author":"Alam","year":"2017","journal-title":"J. Prev Alzheimers Dis."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1093\/brain\/aww330","article-title":"Interleukin-2 improves amyloid pathology, synaptic failure and memory in Alzheimer\u2019s Disease mice","volume":"140","author":"Alves","year":"2017","journal-title":"Brain"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"570586","DOI":"10.3389\/fnmol.2020.570586","article-title":"Functions of P38 MAP kinases in the central nervous system","volume":"13","author":"Asih","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"25226","DOI":"10.1038\/srep25226","article-title":"Neuroprotective effects of the anticancer drug NVP-BEZ235 (Dactolisib) on amyloid-\u03b2 1-42 induced neurotoxicity and memory impairment","volume":"6","author":"Bellozi","year":"2016","journal-title":"Sci. Rep."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.3389\/fphar.2019.01345","article-title":"NVP-BEZ235 (Dactolisib) has protective effects in a transgenic mouse model of Alzheimer\u2019s Disease","volume":"10","author":"Bellozi","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1038\/nrd3531","article-title":"Rapamycin passes the torch: a new generation of MTOR inhibitors","volume":"10","author":"Benjamin","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.neurobiolaging.2004.02.022","article-title":"Secreted \u03b2-amyloid precursor protein activates microglia via JNK and P38-MAPK","volume":"26","author":"Bodles","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1080\/15548627.2019.1615823","article-title":"Rapamycin and Alzheimer Disease: a double-edged sword?","volume":"15","author":"Carosi","year":"2019","journal-title":"Autophagy"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1002\/jnr.24829","article-title":"Extracellular signal-regulated kinase regulates microglial immune responses in Alzheimer\u2019s Disease","volume":"99","author":"Chen","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1186\/s12974-021-02325-6","article-title":"Dysregulated phosphoinositide 3-kinase signaling in microglia: shaping chronic Neuroinflammation","volume":"18","author":"Chu","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.yexmp.2015.07.010","article-title":"IL-9 signaling affects central nervous system resident cells during inflammatory stimuli","volume":"99","author":"Ding","year":"2015","journal-title":"Exp. Mol. Pathol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"441","DOI":"10.3389\/fnins.2020.00441","article-title":"Evaluating the effect of Interleukin-4 in the 3xTg mouse model of Alzheimer\u2019s Disease","volume":"14","author":"Dionisio-Santos","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"P1150","DOI":"10.1016\/j.jalz.2016.07.047","article-title":"P4-304: STAT3 signaling referees microglial amyloid clearance in Alzheimer\u2019S Disease","volume":"12","author":"Doty","year":"2016","journal-title":"Alzheimers Dement."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.bbapap.2009.12.001","article-title":"Dissecting the role of MTOR: lessons from MTOR inhibitors","volume":"1804","author":"Dowling","year":"2010","journal-title":"Biochim. Biophys. Acta."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13024-017-0184-x","article-title":"Late onset Alzheimer\u2019s Disease genetics implicates microglial pathways in Disease risk","volume":"12","author":"Efthymiou","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.neuint.2015.01.007","article-title":"Acetylation and phosphorylation of STAT3 are involved in the responsiveness of microglia to Beta amyloid","volume":"81","author":"Eufemi","year":"2015","journal-title":"Neurochem. Int."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1038\/s41598-017-01868-0","article-title":"Identification and activation of TLR4-mediated Signalling pathways by alginate-derived Guluronate oligosaccharide in RAW264.7 macrophages","volume":"7","author":"Fang","year":"2017","journal-title":"Sci. Rep."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e12445","DOI":"10.1002\/trc2.12445","article-title":"Baricitinib and tofacitinib off-target profile, with a focus on Alzheimer\u2019s disease","volume":"10","author":"Faquetti","year":"2024","journal-title":"Alzheimers Dement (NY)."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"4213","DOI":"10.4049\/jimmunol.1202246","article-title":"IL-4 in the brain: a cytokine to remember","volume":"189","author":"Gadani","year":"2012","journal-title":"J. Immunol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1155\/2015\/361326","article-title":"The critical role of JNK and P38 MAPKs for TLR4 induced microglia-mediated neurotoxicity","volume":"5","author":"Gaikwad","year":"2015","journal-title":"Eur. J. Exp. Biol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"i77","DOI":"10.1136\/ard.2009.119479","article-title":"\u2018Go upstream, young man\u2019: lessons learned from the P38 Saga","volume":"69","author":"Hammaker","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/0165-0173(95)00015-1","article-title":"Interleukin-2 as a Neuroregulatory cytokine","volume":"21","author":"Hanisch","year":"1995","journal-title":"Brain Res. Brain Res. Rev."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"28853","DOI":"10.1074\/jbc.272.46.28853","article-title":"Mouse brain microglia express Interleukin-15 and its Multimeric receptor complex functionally coupled to Janus kinase activity","volume":"272","author":"Hanisch","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.neuroscience.2020.03.008","article-title":"IL-4 switches microglia\/macrophage M1\/M2 polarization and alleviates neurological damage by modulating the JAK1\/STAT6 pathway following ICH","volume":"437","author":"He","year":"2020","journal-title":"Neuroscience"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3389\/fncel.2018.00110","article-title":"Microglial activation after systemic stimulation with lipopolysaccharide and Escherichia Coli","volume":"12","author":"Hoogland","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"113082","DOI":"10.1016\/j.expneurol.2019.113082","article-title":"Deletion of Chitinase-3-like 1 accelerates stroke development through enhancement of Neuroinflammation by STAT6-dependent M2 microglial inactivation in Chitinase-3-like 1 knockout mice","volume":"323","author":"Im","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1016\/S0197-4580(03)00126-X","article-title":"Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1 Beta production","volume":"25","author":"Kim","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a central mechanism in Alzheimer\u2019s Disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/s12974-015-0243-6","article-title":"Determining the role of IL-4 induced Neuroinflammation in microglial activity and amyloid-\u03b2 using BV2 microglial cells and APP\/PS1 transgenic mice","volume":"12","author":"Latta","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"3588","DOI":"10.3390\/cells11223588","article-title":"Abrocitinib attenuates microglia-mediated Neuroinflammation after traumatic brain injury via inhibiting the JAK1\/STAT1\/NF-\u039aB pathway","volume":"11","author":"Li","year":"2022","journal-title":"Cells"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1161\/ATVBAHA.118.310958","article-title":"Novel Antiatherosclerotic therapies","volume":"39","author":"Libby","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/bies.10204","article-title":"Activation of the JNK signaling pathway: breaking the brake on apoptosis","volume":"25","author":"Lin","year":"2003","journal-title":"Bioessays"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"e25416","DOI":"10.1371\/journal.pone.0025416","article-title":"Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits","volume":"6","author":"Majumder","year":"2011","journal-title":"PLoS One"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.cell.2017.04.001","article-title":"AKT\/PKB signaling: navigating the network","volume":"169","author":"Manning","year":"2017","journal-title":"Cell"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1201982","DOI":"10.3389\/fnagi.2023.1201982","article-title":"Microglia in Alzheimer\u2019s Disease: pathogenesis, mechanisms, and therapeutic potentials","volume":"15","author":"Miao","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"e041019","DOI":"10.1002\/alz.041019","article-title":"STAT3 inhibition reverses Neuroinflammation and A\u03b2 metabolism induced by systemic inflammation","volume":"16","author":"Millot","year":"2020","journal-title":"Alzheimers Dement."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"a011254","DOI":"10.1101\/cshperspect.a011254","article-title":"MAP kinase pathways","volume":"4","author":"Morrison","year":"2012","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1093\/oxfordjournals.jbchem.a002969","article-title":"Microglia: activation and their significance in the central nervous system","volume":"130","author":"Nakajima","year":"2001","journal-title":"J. Biochem."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"195.e1","DOI":"10.1016\/j.neurobiolaging.2010.05.008","article-title":"Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function","volume":"33","author":"Njie","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"4739","DOI":"10.3390\/ijms24054739","article-title":"The pathological activation of microglia is modulated by sexually dimorphic pathways","volume":"24","author":"O\u2019Connor","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.brainresbull.2023.02.008","article-title":"Chromosomal and gonadal factors regulate microglial sex effects in the aging brain","volume":"195","author":"Oca\u00f1as","year":"2023","journal-title":"Brain Res. Bull."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"3926","DOI":"10.4049\/jimmunol.1800097","article-title":"Identification of cellular sources of IL2 needed for regulatory T cell development and homeostasis","volume":"200","author":"Owen","year":"2018","journal-title":"J. Immunol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.neubiorev.2012.11.009","article-title":"Brain Interleukin-15 in Neuroinflammation and behavior","volume":"37","author":"Pan","year":"2013","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"2130","DOI":"10.1038\/s41598-022-05980-8","article-title":"P38 activation occurs mainly in microglia in the P301S Tauopathy mouse model","volume":"12","author":"Perea","year":"2022","journal-title":"Sci. Rep."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"5925","DOI":"10.3390\/ijms24065925","article-title":"Immune regulatory functions of macrophages and microglia in central nervous system diseases","volume":"24","author":"Poppell","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00109-013-1090-5","article-title":"The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia","volume":"92","author":"Przanowski","year":"2014","journal-title":"J. Mol. Med. (Berl)"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.3390\/brainsci12091153","article-title":"Regulation of microglia-activation-mediated Neuroinflammation to ameliorate ischemia-reperfusion injury via the STAT5-NF-\u039aB pathway in ischemic stroke","volume":"12","author":"Pu","year":"2022","journal-title":"Brain Sci."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1007\/s12192-021-01231-3","article-title":"The PI3K\/Akt signaling Axis in Alzheimer\u2019s Disease: a valuable target to stimulate or suppress?","volume":"26","author":"Razani","year":"2021","journal-title":"Cell Stress Chaperones"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"e512","DOI":"10.1212\/NXG.0000000000000512","article-title":"Late-onset vs Nonmendelian early-onset Alzheimer Disease","volume":"6","author":"Reitz","year":"2020","journal-title":"Neurol. Gen."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1021\/acschemneuro.5b00002","article-title":"Targeting human central nervous system protein kinases: an isoform selective P38\u03b1MAPK inhibitor that attenuates Disease progression in Alzheimer\u2019s Disease mouse models","volume":"6","author":"Roy","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.neurobiolaging.2018.06.006","article-title":"An isoform-selective P38\u03b1 mitogen-activated protein kinase inhibitor rescues early entorhinal cortex dysfunctions in a mouse model of Alzheimer\u2019s Disease","volume":"70","author":"Rutigliano","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s43556-023-00151-1","article-title":"JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions","volume":"4","author":"Sarapultsev","year":"2023","journal-title":"Molecular Biomedicine"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1002\/acn3.549","article-title":"An exploratory clinical study of P38\u03b1 kinase inhibition in Alzheimer\u2019s Disease","volume":"5","author":"Scheltens","year":"2018","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"a006189","DOI":"10.1101\/cshperspect.a006189","article-title":"Neuropathological alterations in Alzheimer Disease","volume":"1","author":"Serrano-Pozo","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"5294","DOI":"10.1523\/JNEUROSCI.2427-21.2022","article-title":"Microglial MTOR activation upregulates Trem2 and enhances \u03b2-amyloid plaque clearance in the 5XFAD Alzheimer\u2019s Disease model","volume":"42","author":"Shi","year":"2022","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1161\/STROKEAHA.119.028638","article-title":"IL (interleukin)-15 bridges astrocyte-microglia crosstalk and exacerbates brain injury following intracerebral hemorrhage","volume":"51","author":"Shi","year":"2020","journal-title":"Stroke"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1021\/acschemneuro.3c00093","article-title":"JNK activation in Alzheimer\u2019s Disease is driven by amyloid \u03b2 and is associated with tau pathology","volume":"14","author":"Solas","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.joca.2020.02.027","article-title":"The PI3K\/AKT\/MTOR signaling pathway in osteoarthritis: a narrative review","volume":"28","author":"Sun","year":"2020","journal-title":"Osteoarthr. Cartil."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.bbr.2018.02.015","article-title":"Neuroinflammation in Alzheimer\u2019s Disease: pleiotropic roles for cytokines and neuronal Pentraxins","volume":"347","author":"Swanson","year":"2018","journal-title":"Behav. Brain Res."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.neurobiolaging.2018.12.019","article-title":"Proinflammatory and anti-inflammatory cytokines in the CSF of patients with Alzheimer\u2019s Disease and their correlation with cognitive decline","volume":"76","author":"Taipa","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.3233\/JAD-161088","article-title":"Oxidative stress, synaptic dysfunction, and Alzheimer\u2019s Disease","volume":"57","author":"T\u00f6nnies","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"105303","DOI":"10.1016\/j.nbd.2021.105303","article-title":"INPP5D expression is associated with risk for Alzheimer\u2019s Disease and induced by plaque-associated microglia","volume":"153","author":"Tsai","year":"2021","journal-title":"Neurobiol. Dis."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1038\/s41380-022-01912-0","article-title":"Hydroxychloroquine lowers Alzheimer\u2019s Disease and related dementias risk and rescues molecular phenotypes related to Alzheimer\u2019s Disease","volume":"28","author":"Varma","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1002\/ana.25543","article-title":"IL-9 alterations linked to Alzheimer\u2019s Disease in African Americans","volume":"86","author":"Wharton","year":"2019","journal-title":"Ann. Neurol."},{"key":"ref66","unstructured":"Dementia\n          \n          \n          \n          2023"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.cell.2020.02.013","article-title":"Repopulating microglia promote brain repair in an IL-6-dependent manner","volume":"180","author":"Willis","year":"2020","journal-title":"Cell"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1002\/glia.10314","article-title":"Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and P38","volume":"45","author":"Xie","year":"2004","journal-title":"Glia"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.neurobiolaging.2019.06.003","article-title":"Targeted genetic analysis of cerebral blood flow imaging phenotypes implicates the INPP5D gene","volume":"81","author":"Yao","year":"2019","journal-title":"Neurobiol. Aging"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"687","DOI":"10.3233\/JAD-161211","article-title":"INPP5D MRNA expression and cognitive decline in Japanese Alzheimer\u2019s Disease subjects","volume":"58","author":"Yoshino","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1038\/s41590-022-01208-z","article-title":"Astrocyte-targeted gene delivery of interleukin 2 specifically increases brain-resident regulatory T cell numbers and protects against pathological Neuroinflammation","volume":"23","author":"Yshii","year":"2022","journal-title":"Nat. Immunol."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/s41401-021-00778-2","article-title":"HACE1 negatively regulates Neuroinflammation through Ubiquitylating and degrading Rac1 in Parkinson\u2019s Disease models","volume":"43","author":"Zang","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2012.01.005","article-title":"MTOR inhibitors in Cancer therapy","volume":"319","author":"Zaytseva","year":"2012","journal-title":"Cancer Lett."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"11281","DOI":"10.1523\/JNEUROSCI.1685-15.2015","article-title":"Neuronal Interleukin-4 as a modulator of microglial pathways and ischemic brain damage","volume":"35","author":"Zhao","year":"2015","journal-title":"J. Neurosci."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12974-017-0845-2","article-title":"Retention of Normal glia function by an isoform-selective protein kinase inhibitor drug candidate that modulates cytokine production and cognitive outcomes","volume":"14","author":"Zhou","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"771453","DOI":"10.3389\/fimmu.2021.771453","article-title":"Exposure of microglia to Interleukin-4 represses NF-\u039aB-dependent transcription of toll-like receptor-induced cytokines","volume":"12","author":"Zuiderwijk-Sick","year":"2021","journal-title":"Front. Immunol."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2024.1441691\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T05:11:34Z","timestamp":1726031494000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2024.1441691\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,11]]},"references-count":76,"alternative-id":["10.3389\/fnmol.2024.1441691"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2024.1441691","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,11]]},"article-number":"1441691"}}