{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T15:42:41Z","timestamp":1792856561288,"version":"4.5.0"},"reference-count":120,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T00:00:00Z","timestamp":1636675200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurodegenerative diseases are characterized by chronic neuroinflammation and may perpetuate ongoing fibrotic reactions within the central nervous system. Unfortunately, there is no therapeutic available that treats neurodegenerative inflammation and its sequelae. Here we utilize cromolyn, a mast cell inhibitor with anti-inflammatory capabilities, and its fluorinated analogue F-cromolyn to study fibrosis-related protein regulation and secretion downstream of neuroinflammation and their ability to promote microglial phagocytosis and neurite outgrowth. In this report, RNA-seq analysis shows that administration of the pro-inflammatory cytokine TNF-\u03b1 to HMC3 human microglia results in a robust upregulation of fibrosis-associated genes. Subsequent treatment with cromolyn and F-cromolyn resulted in reduced secretion of collagen XVIII, fibronectin, and tenascin-c. Additionally, we show that cromolyn and F-cromolyn reduce pro-inflammatory proteins PLP1, PELP1, HSP90, IL-2, GRO-\u03b1, Eotaxin, and VEGF-\u0391, while promoting secretion of anti-inflammatory IL-4 in HMC3 microglia. Furthermore, cromolyn and F-cromolyn augment neurite outgrowth in PC12 neuronal cells in concert with nerve growth factor. Treatment also differentially altered secretion of neurogenesis-related proteins TTL, PROX1, Rab35, and CSDE1 in HMC3 microglia. Finally, iPSC-derived human microglia more readily phagocytose A\u03b242 with cromolyn and F-cromolyn relative to controls. We propose the cromolyn platform targets multiple proteins upstream of PI3K\/Akt\/mTOR, NF-\u03baB, and GSK-3\u03b2 signaling pathways to affect cytokine, chemokine, and fibrosis-related protein expression.<\/jats:p>","DOI":"10.1038\/s41598-021-00465-6","type":"journal-article","created":{"date-parts":[[2021,11,12]],"date-time":"2021-11-12T06:02:44Z","timestamp":1636696964000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Cromolyn platform suppresses fibrosis and inflammation, promotes microglial phagocytosis and neurite outgrowth"],"prefix":"10.1038","volume":"11","author":[{"given":"Yi-Jun","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Downey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungwoon","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Shoup","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Elmaleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,12]]},"reference":[{"key":"465_CR1","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1111\/imm.12922","volume":"154","author":"J Stephenson","year":"2018","unstructured":"Stephenson, J., Nutma, E., van der Valk, P. & Amor, S. Inflammation in CNS neurodegenerative diseases. Immunology 154, 204\u2013219 (2018).","journal-title":"Immunology"},{"key":"465_CR2","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1113\/JP272134","volume":"595","author":"TL Tay","year":"2017","unstructured":"Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K. & Tremblay, M. -\u00c8. Microglia across the lifespan: From origin to function in brain development, plasticity and cognition. J. Physiol. 595, 1929\u20131945 (2017).","journal-title":"J. Physiol."},{"key":"465_CR3","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s12974-019-1586-1","volume":"16","author":"T Chu","year":"2019","unstructured":"Chu, T. et al. Dynamic response of microglia\/macrophage polarization following demyelination in mice. J. Neuroinflam. 16, 188 (2019).","journal-title":"J. Neuroinflam."},{"key":"465_CR4","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","volume":"35","author":"M Colonna","year":"2017","unstructured":"Colonna, M. & Butovsky, O. Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 35, 441\u2013468 (2017).","journal-title":"Annu. Rev. Immunol."},{"key":"465_CR5","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1093\/brain\/awv066","volume":"138","author":"MA Michell-Robinson","year":"2015","unstructured":"Michell-Robinson, M. A. et al. Roles of microglia in brain development, tissue maintenance and repair. Brain 138, 1138\u20131159 (2015).","journal-title":"Brain"},{"key":"465_CR6","doi-asserted-by":"crossref","unstructured":"Crapser, J. D. et al. Microglia facilitate loss of perineuronal nets in the Alzheimer\u2019s disease brain. EBioMedicine 58, 102919 (2020).","DOI":"10.1016\/j.ebiom.2020.102919"},{"key":"465_CR7","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.cell.2020.05.050","volume":"182","author":"PT Nguyen","year":"2020","unstructured":"Nguyen, P. T. et al. Microglial remodeling of the extracellular matrix promotes synapse plasticity. Cell 182, 388-403.e15 (2020).","journal-title":"Cell"},{"key":"465_CR8","doi-asserted-by":"publisher","first-page":"3974","DOI":"10.1523\/JNEUROSCI.4363-08.2009","volume":"29","author":"H Wake","year":"2009","unstructured":"Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S. & Nabekura, J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29, 3974 (2009).","journal-title":"J. Neurosci."},{"key":"465_CR9","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3389\/fncel.2018.00323","volume":"12","author":"Z Szepesi","year":"2018","unstructured":"Szepesi, Z., Manouchehrian, O., Bachiller, S. & Deierborg, T. Bidirectional microglia-neuron communication in health and disease. Front. Cell. Neurosci. 12, 323 (2018).","journal-title":"Front. Cell. Neurosci."},{"key":"465_CR10","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1016\/j.ajpath.2011.08.036","volume":"179","author":"A Aldrich","year":"2011","unstructured":"Aldrich, A. & Kielian, T. Central nervous system fibrosis is associated with fibrocyte-like infiltrates. Am. J. Pathol. 179, 2952\u20132962 (2011).","journal-title":"Am. J. Pathol."},{"key":"465_CR11","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3389\/fncel.2020.00078","volume":"14","author":"T Yang","year":"2020","unstructured":"Yang, T., Dai, Y., Chen, G. & Cui, S. Dissecting the dual role of the glial scar and scar-forming astrocytes in spinal cord injury. Front. Cell. Neurosci. 14, 78 (2020).","journal-title":"Front. Cell. Neurosci."},{"key":"465_CR12","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1126\/science.1203165","volume":"333","author":"C G\u00f6ritz","year":"2011","unstructured":"G\u00f6ritz, C. et al. A pericyte origin of spinal cord scar tissue. Science 333, 238\u2013242 (2011).","journal-title":"Science"},{"key":"465_CR13","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1016\/j.matbio.2018.02.009","volume":"68\u201369","author":"DO Dias","year":"2018","unstructured":"Dias, D. O. & G\u00f6ritz, C. Fibrotic scarring following lesions to the central nervous system. Matrix Biol. 68\u201369, 561\u2013570 (2018).","journal-title":"Matrix Biol."},{"key":"465_CR14","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1186\/1742-2094-11-104","volume":"11","author":"D Jansson","year":"2014","unstructured":"Jansson, D. et al. A role for human brain pericytes in neuroinflammation. J. Neuroinflam. 11, 104 (2014).","journal-title":"J. Neuroinflam."},{"key":"465_CR15","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.3389\/fphar.2019.01140","volume":"10","author":"J Dong","year":"2019","unstructured":"Dong, J. & Ma, Q. In vivo activation and pro-fibrotic function of NF-\u03baB in fibroblastic cells during pulmonary inflammation and fibrosis induced by carbon nanotubes. Front. Pharmacol. 10, 1140 (2019).","journal-title":"Front. Pharmacol."},{"key":"465_CR16","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","volume":"541","author":"SA Liddelow","year":"2017","unstructured":"Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481\u2013487 (2017).","journal-title":"Nature"},{"key":"465_CR17","doi-asserted-by":"publisher","first-page":"E1896","DOI":"10.1073\/pnas.1800165115","volume":"115","author":"LE Clarke","year":"2018","unstructured":"Clarke, L. E. et al. Normal aging induces A1-like astrocyte reactivity. Proc. Natl. Acad. Sci. USA 115, E1896 (2018).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"465_CR18","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41593-020-00770-9","volume":"24","author":"CE Dorrier","year":"2021","unstructured":"Dorrier, C. E. et al. CNS fibroblasts form a fibrotic scar in response to immune cell infiltration. Nat. Neurosci. 24, 234\u2013244 (2021).","journal-title":"Nat. Neurosci."},{"key":"465_CR19","doi-asserted-by":"publisher","first-page":"8054","DOI":"10.1038\/s41598-021-85702-8","volume":"11","author":"Y-J Wang","year":"2021","unstructured":"Wang, Y.-J., Monteagudo, A., Downey, M. A., Ashton-Rickardt, P. G. & Elmaleh, D. R. Cromolyn inhibits the secretion of inflammatory cytokines by human microglia (HMC3). Sci. Rep. 11, 8054 (2021).","journal-title":"Sci. Rep."},{"key":"465_CR20","doi-asserted-by":"publisher","first-page":"8500","DOI":"10.1523\/JNEUROSCI.2451-04.2004","volume":"24","author":"A Rappert","year":"2004","unstructured":"Rappert, A. et al. CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion. J. Neurosci. 24, 8500 (2004).","journal-title":"J. Neurosci."},{"key":"465_CR21","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1172\/JCI1422","volume":"101","author":"S Qin","year":"1998","unstructured":"Qin, S. et al. The chemokine receptors CXCR3 and CCR5 mark subsets of T cells associated with certain inflammatory reactions. J. Clin. Invest. 101, 746\u2013754 (1998).","journal-title":"J. Clin. Invest."},{"key":"465_CR22","doi-asserted-by":"publisher","first-page":"251","DOI":"10.3389\/fnagi.2014.00251","volume":"6","author":"AWJ Morris","year":"2014","unstructured":"Morris, A. W. J., Carare, R. O., Schreiber, S. & Hawkes, C. A. The cerebrovascular basement membrane: Role in the clearance of \u03b2-amyloid and cerebral amyloid angiopathy. Front. Aging Neurosci. 6, 251\u2013251 (2014).","journal-title":"Front. Aging Neurosci."},{"key":"465_CR23","doi-asserted-by":"publisher","first-page":"1651157","DOI":"10.1080\/21688370.2019.1651157","volume":"7","author":"MJ Reed","year":"2019","unstructured":"Reed, M. J., Damodarasamy, M. & Banks, W. A. The extracellular matrix of the blood\u2013brain barrier: Structural and functional roles in health, aging, and Alzheimer\u2019s disease. Tissue Barriers 7, 1651157 (2019).","journal-title":"Tissue Barriers"},{"key":"465_CR24","doi-asserted-by":"publisher","first-page":"14527","DOI":"10.1038\/srep14527","volume":"5","author":"A Bikbaev","year":"2015","unstructured":"Bikbaev, A., Frischknecht, R. & Heine, M. Brain extracellular matrix retains connectivity in neuronal networks. Sci. Rep. 5, 14527 (2015).","journal-title":"Sci. Rep."},{"key":"465_CR25","first-page":"76","volume":"2","author":"MJ V\u00e9gh","year":"2014","unstructured":"V\u00e9gh, M. J. et al. Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer\u2019s disease. Acta Neuropathol. Commun. 2, 76 (2014).","journal-title":"Acta Neuropathol. Commun."},{"key":"465_CR26","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/nan.12295","volume":"43","author":"F-X Lepelletier","year":"2017","unstructured":"Lepelletier, F.-X., Mann, D. M. A., Robinson, A. C., Pinteaux, E. & Boutin, H. Early changes in extracellular matrix in Alzheimer\u2019s disease. Neuropathol. Appl. Neurobiol. 43, 167\u2013182 (2017).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"465_CR27","doi-asserted-by":"publisher","first-page":"3850","DOI":"10.4049\/jimmunol.170.7.3850","volume":"170","author":"R Milner","year":"2003","unstructured":"Milner, R. & Campbell, I. L. The extracellular matrix and cytokines regulate microglial integrin expression and activation. J. Immunol. 170, 3850\u20133858 (2003).","journal-title":"J. Immunol."},{"key":"465_CR28","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1002\/glia.23894","volume":"69","author":"S Stoyanov","year":"2021","unstructured":"Stoyanov, S. et al. Attenuation of the extracellular matrix restores microglial activity during the early stage of amyloidosis. Glia 69, 182\u2013200 (2021).","journal-title":"Glia"},{"key":"465_CR29","doi-asserted-by":"publisher","first-page":"5816","DOI":"10.1038\/s41467-019-13812-z","volume":"10","author":"K Haruwaka","year":"2019","unstructured":"Haruwaka, K. et al. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat. Commun. 10, 5816 (2019).","journal-title":"Nat. Commun."},{"key":"465_CR30","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","volume":"119","author":"MV Sofroniew","year":"2010","unstructured":"Sofroniew, M. V. & Vinters, H. V. Astrocytes: Biology and pathology. Acta Neuropathol. 119, 7\u201335 (2010).","journal-title":"Acta Neuropathol."},{"key":"465_CR31","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.expneurol.2014.01.001","volume":"258","author":"KA Kigerl","year":"2014","unstructured":"Kigerl, K. A., de Rivero Vaccari, J. P., Dietrich, W. D., Popovich, P. G. & Keane, R. W. Pattern recognition receptors and central nervous system repair. Exp. Neurol. 258, 5\u201316 (2014).","journal-title":"Exp. Neurol."},{"key":"465_CR32","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1161\/CIRCULATIONAHA.118.034609","volume":"138","author":"I Valiente-Alandi","year":"2018","unstructured":"Valiente-Alandi, I. et al. Inhibiting fibronectin attenuates fibrosis and improves cardiac function in a model of heart failure. Circulation 138, 1236\u20131252 (2018).","journal-title":"Circulation"},{"key":"465_CR33","doi-asserted-by":"publisher","first-page":"11703","DOI":"10.1038\/ncomms11703","volume":"7","author":"S Bhattacharyya","year":"2016","unstructured":"Bhattacharyya, S. et al. Tenascin-C drives persistence of organ fibrosis. Nat. Commun. 7, 11703 (2016).","journal-title":"Nat. Commun."},{"key":"465_CR34","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1002\/jnr.21552","volume":"86","author":"M-C Seo","year":"2008","unstructured":"Seo, M.-C. et al. Discoidin domain receptor 1 mediates collagen-induced inflammatory activation of microglia in culture. J. Neurosci. Res. 86, 1087\u20131095 (2008).","journal-title":"J. Neurosci. Res."},{"key":"465_CR35","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.3390\/ijms20205086","volume":"20","author":"J Etich","year":"2019","unstructured":"Etich, J. et al. Gene expression profiling of the extracellular matrix signature in macrophages of different activation status: relevance for skin wound healing. Int. J. Mol. Sci. 20, 5086 (2019).","journal-title":"Int. J. Mol. Sci."},{"key":"465_CR36","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1186\/s12931-019-1118-7","volume":"20","author":"LA Organ","year":"2019","unstructured":"Organ, L. A. et al. Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort. Respir. Res. 20, 148 (2019).","journal-title":"Respir. Res."},{"key":"465_CR37","doi-asserted-by":"publisher","first-page":"e175","DOI":"10.1016\/S2665-9913(20)30385-4","volume":"3","author":"R Dobrota","year":"2021","unstructured":"Dobrota, R. et al. Circulating collagen neo-epitopes and their role in the prediction of fibrosis in patients with systemic sclerosis: a multicentre cohort study. Lancet Rheumatol. 3, e175\u2013e184 (2021).","journal-title":"Lancet Rheumatol."},{"key":"465_CR38","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1074\/jbc.M114.586602","volume":"290","author":"Y Hori","year":"2015","unstructured":"Hori, Y. et al. A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid beta in the brain in a transgenic model of Alzheimer disease. J. Biol. Chem. 290, 1966\u20131978 (2015).","journal-title":"J. Biol. Chem."},{"key":"465_CR39","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1038\/s41598-018-19641-2","volume":"8","author":"C Zhang","year":"2018","unstructured":"Zhang, C. et al. Cromolyn reduces levels of the Alzheimer\u2019s disease-associated amyloid \u03b2-protein by promoting microglial phagocytosis. Sci. Rep. 8, 1144 (2018).","journal-title":"Sci. Rep."},{"key":"465_CR40","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1007\/s40261-017-0549-5","volume":"37","author":"D Brazier","year":"2017","unstructured":"Brazier, D., Perry, R., Keane, J., Barrett, K. & Elmaleh, D. R. Pharmacokinetics of cromolyn and ibuprofen in healthy elderly volunteers. Clin. Drug Investig. 37, 1025\u20131034 (2017).","journal-title":"Clin. Drug Investig."},{"key":"465_CR41","doi-asserted-by":"publisher","first-page":"775","DOI":"10.3233\/JAD-201419","volume":"80","author":"TM Shoup","year":"2021","unstructured":"Shoup, T. M. et al. Evaluation of fluorinated cromolyn derivatives as potential therapeutics for Alzheimer\u2019s disease. J. Alzheimers Dis. 80, 775\u2013786 (2021).","journal-title":"J. Alzheimers Dis."},{"key":"465_CR42","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.1074\/mcp.RA117.000314","volume":"16","author":"R Bruderer","year":"2017","unstructured":"Bruderer, R. et al. Optimization of experimental parameters in data-independent mass spectrometry significantly increases depth and reproducibility of results. Mol. Cell Proteom. 16, 2296\u20132309 (2017).","journal-title":"Mol. Cell Proteom."},{"key":"465_CR43","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1021\/pr050300l","volume":"5","author":"SJ Callister","year":"2006","unstructured":"Callister, S. J. et al. Normalization approaches for removing systematic biases associated with mass spectrometry and label-free proteomics. J. Proteome Res. 5, 277\u2013286 (2006).","journal-title":"J. Proteome Res."},{"key":"465_CR44","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1242\/dmm.004077","volume":"4","author":"TR Cox","year":"2011","unstructured":"Cox, T. R. & Erler, J. T. Remodeling and homeostasis of the extracellular matrix: Implications for fibrotic diseases and cancer. Dis. Model Mech. 4, 165\u2013178 (2011).","journal-title":"Dis. Model Mech."},{"key":"465_CR45","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.1042\/BST0361398","volume":"36","author":"A Gursoy","year":"2008","unstructured":"Gursoy, A., Keskin, O. & Nussinov, R. Topological properties of protein interaction networks from a structural perspective. Biochem. Soc. Trans. 36, 1398\u20131403 (2008).","journal-title":"Biochem. Soc. Trans."},{"key":"465_CR46","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1146\/annurev-immunol-042617-053352","volume":"36","author":"SH Ross","year":"2018","unstructured":"Ross, S. H. & Cantrell, D. A. Signaling and function of interleukin-2 in T lymphocytes. Annu. Rev. Immunol. 36, 411\u2013433 (2018).","journal-title":"Annu. Rev. Immunol."},{"key":"465_CR47","doi-asserted-by":"publisher","first-page":"5603","DOI":"10.4049\/jimmunol.151.10.5603","volume":"151","author":"RP Donnelly","year":"1993","unstructured":"Donnelly, R. P. et al. Tissue-specific regulation of IL-6 production by IL-4. Differential effects of IL-4 on nuclear factor-kappa B activity in monocytes and fibroblasts. J. Immunol. 151, 5603\u20135612 (1993).","journal-title":"J. Immunol."},{"key":"465_CR48","doi-asserted-by":"publisher","first-page":"14234","DOI":"10.1523\/JNEUROSCI.1523-15.2015","volume":"35","author":"M Usenovic","year":"2015","unstructured":"Usenovic, M. et al. Internalized tau oligomers cause neurodegeneration by inducing accumulation of pathogenic tau in human neurons derived from induced pluripotent stem cells. J. Neurosci. 35, 14234 (2015).","journal-title":"J. Neurosci."},{"key":"465_CR49","doi-asserted-by":"publisher","first-page":"37829","DOI":"10.1074\/jbc.M003146200","volume":"275","author":"AL Hughes","year":"2000","unstructured":"Hughes, A. L., Gollapudi, L., Sladek, T. L. & Neet, K. E. Mediation of nerve growth factor-driven cell cycle arrest in PC12 cells by p53. J. Biol. Chem. 275, 37829\u201337837 (2000).","journal-title":"J. Biol. Chem."},{"key":"465_CR50","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.brainres.2018.05.023","volume":"1692","author":"S Li","year":"2018","unstructured":"Li, S. et al. Histone deacetylase 1 promotes glioblastoma cell proliferation and invasion via activation of PI3K\/AKT and MEK\/ERK signaling pathways. Brain Res. 1692, 154\u2013162 (2018).","journal-title":"Brain Res."},{"key":"465_CR51","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.immuni.2018.02.016","volume":"48","author":"M Datta","year":"2018","unstructured":"Datta, M. et al. Histone deacetylases 1 and 2 regulate microglia function during development, homeostasis, and neurodegeneration in a context-dependent manner. Immunity 48, 514-529.e6 (2018).","journal-title":"Immunity"},{"key":"465_CR52","doi-asserted-by":"publisher","first-page":"22913","DOI":"10.1074\/jbc.M116.729038","volume":"291","author":"LS Wylezinski","year":"2016","unstructured":"Wylezinski, L. S. & Hawiger, J. Interleukin 2 activates brain microvascular endothelial cells resulting in destabilization of adherens junctions *. J. Biol. Chem. 291, 22913\u201322923 (2016).","journal-title":"J. Biol. Chem."},{"key":"465_CR53","doi-asserted-by":"publisher","first-page":"11281","DOI":"10.1523\/JNEUROSCI.1685-15.2015","volume":"35","author":"X Zhao","year":"2015","unstructured":"Zhao, X. et al. Neuronal interleukin-4 as a modulator of microglial pathways and ischemic brain damage. J. Neurosci. 35, 11281 (2015).","journal-title":"J. Neurosci."},{"key":"465_CR54","doi-asserted-by":"publisher","first-page":"e72744","DOI":"10.1371\/journal.pone.0072744","volume":"8","author":"K Zhang","year":"2013","unstructured":"Zhang, K. et al. CXCL1 contributes to \u03b2-amyloid-induced transendothelial migration of monocytes in Alzheimer\u2019s disease. PLoS ONE 8, e72744 (2013).","journal-title":"PLoS ONE"},{"key":"465_CR55","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1186\/1742-2094-8-41","volume":"8","author":"EA Johnson","year":"2011","unstructured":"Johnson, E. A. et al. Increased expression of the chemokines CXCL1 and MIP-1\u03b1 by resident brain cells precedes neutrophil infiltration in the brain following prolonged soman-induced status epilepticus in rats. J. Neuroinflam. 8, 41 (2011).","journal-title":"J. Neuroinflam."},{"key":"465_CR56","doi-asserted-by":"publisher","first-page":"33123","DOI":"10.1038\/srep33123","volume":"6","author":"KV Sawant","year":"2016","unstructured":"Sawant, K. V. et al. Chemokine CXCL1 mediated neutrophil recruitment: Role of glycosaminoglycan interactions. Sci. Rep. 6, 33123 (2016).","journal-title":"Sci. Rep."},{"key":"465_CR57","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1002\/glia.22892","volume":"63","author":"B Parajuli","year":"2015","unstructured":"Parajuli, B., Horiuchi, H., Mizuno, T., Takeuchi, H. & Suzumura, A. CCL11 enhances excitotoxic neuronal death by producing reactive oxygen species in microglia. Glia 63, 2274\u20132284 (2015).","journal-title":"Glia"},{"key":"465_CR58","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/S0197-4580(01)00285-8","volume":"23","author":"E Tarkowski","year":"2002","unstructured":"Tarkowski, E. et al. Increased intrathecal levels of the angiogenic factors VEGF and TGF-beta in Alzheimer\u2019s disease and vascular dementia. Neurobiol. Aging 23, 237\u2013243 (2002).","journal-title":"Neurobiol. Aging"},{"key":"465_CR59","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1089\/rej.2006.9.485","volume":"9","author":"M Chiappelli","year":"2006","unstructured":"Chiappelli, M. et al. VEGF gene and phenotype relation with Alzheimer\u2019s disease and mild cognitive impairment. Rejuvenat. Res. 9, 485\u2013493 (2006).","journal-title":"Rejuvenat. Res."},{"key":"465_CR60","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1186\/s12886-018-0886-z","volume":"18","author":"X Ding","year":"2018","unstructured":"Ding, X. et al. Microglia enhanced the angiogenesis, migration and proliferation of co-cultured RMECs. BMC Ophthalmol. 18, 249\u2013249 (2018).","journal-title":"BMC Ophthalmol."},{"key":"465_CR61","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1093\/brain\/awf043","volume":"125","author":"JY Garbern","year":"2002","unstructured":"Garbern, J. Y. et al. Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation. Brain 125, 551\u2013561 (2002).","journal-title":"Brain"},{"key":"465_CR62","doi-asserted-by":"publisher","first-page":"AN20100016","DOI":"10.1042\/AN20100016","volume":"2","author":"CL Tatar","year":"2010","unstructured":"Tatar, C. L. et al. Increased Plp1 gene expression leads to massive microglial cell activation and inflammation throughout the brain. ASN Neuro 2, AN20100016 (2010).","journal-title":"ASN Neuro"},{"key":"465_CR63","doi-asserted-by":"publisher","first-page":"e12484","DOI":"10.1111\/jne.12484","volume":"30","author":"R Thakkar","year":"2018","unstructured":"Thakkar, R. et al. PELP1: A key mediator of estrogen signaling and actions in the brain. J. Neuroendocrinol. 30, e12484 (2018).","journal-title":"J. Neuroendocrinol."},{"key":"465_CR64","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1074\/jbc.M116.739847","volume":"292","author":"BJ Girard","year":"2017","unstructured":"Girard, B. J. et al. Cytoplasmic localization of proline, glutamic acid, leucine-rich protein 1 (PELP1) induces breast epithelial cell migration through up-regulation of inhibitor of \u03baB Kinase \u03f5 and inflammatory cross-talk with macrophages. J. Biol. Chem. 292, 339\u2013350 (2017).","journal-title":"J. Biol. Chem."},{"key":"465_CR65","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/mc.23152","volume":"59","author":"Y Luo","year":"2020","unstructured":"Luo, Y. et al. PELP1 signaling contributes to medulloblastoma progression by regulating the NF-\u03baB pathway. Mol. Carcinog. 59, 281\u2013292 (2020).","journal-title":"Mol. Carcinog."},{"key":"465_CR66","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1002\/jnr.23288","volume":"92","author":"A Langenfurth","year":"2014","unstructured":"Langenfurth, A. et al. Membrane-type 1 metalloproteinase is upregulated in microglia\/brain macrophages in neurodegenerative and neuroinflammatory diseases. J. Neurosci. Res. 92, 275\u2013286 (2014).","journal-title":"J. Neurosci. Res."},{"key":"465_CR67","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.gene.2016.03.017","volume":"585","author":"GR Sareddy","year":"2016","unstructured":"Sareddy, G. R. & Vadlamudi, R. K. PELP1: Structure, biological function and clinical significance. Gene 585, 128\u2013134 (2016).","journal-title":"Gene"},{"key":"465_CR68","doi-asserted-by":"publisher","first-page":"51","DOI":"10.3390\/i8010060","volume":"8","author":"F Dou","year":"2007","unstructured":"Dou, F., Chang, X. & Ma, D. Hsp90 maintains the stability and function of the tau phosphorylating kinase GSK3\u03b2. Int. J. Mol. Sci. 8, 51\u201360 (2007).","journal-title":"Int. J. Mol. Sci."},{"key":"465_CR69","doi-asserted-by":"publisher","first-page":"10832","DOI":"10.1073\/pnas.170276797","volume":"97","author":"S Sato","year":"2000","unstructured":"Sato, S., Fujita, N. & Tsuruo, T. Modulation of Akt kinase activity by binding to Hsp90. Proc. Natl. Acad. Sci. USA 97, 10832\u201310837 (2000).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"465_CR70","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1158\/1535-7163.MCT-16-0848","volume":"16","author":"L Giulino-Roth","year":"2017","unstructured":"Giulino-Roth, L. et al. Inhibition of Hsp90 suppresses PI3K\/AKT\/mTOR signaling and has antitumor activity in burkitt lymphoma. Mol. Cancer Ther. 16, 1779 (2017).","journal-title":"Mol. Cancer Ther."},{"key":"465_CR71","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/S0014-5793(04)00229-7","volume":"562","author":"A Subbarao Sreedhar","year":"2004","unstructured":"Subbarao Sreedhar, A., Kalm\u00e1r, \u00c9., Csermely, P. & Shen, Y.-F. Hsp90 isoforms: Functions, expression and clinical importance. FEBS Lett. 562, 11\u201315 (2004).","journal-title":"FEBS Lett."},{"key":"465_CR72","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.biocel.2018.11.003","volume":"106","author":"G-L He","year":"2019","unstructured":"He, G.-L. et al. Inhibition of HSP90\u03b2 by ganetespib blocks the microglial signalling of evoked pro-inflammatory responses to heat shock. Int. J. Biochem. Cell Biol. 106, 35\u201345 (2019).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"465_CR73","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1097\/01.MIB.0000442839.28664.75","volume":"20","author":"CB Collins","year":"2014","unstructured":"Collins, C. B. et al. Targeted inhibition of heat shock protein 90 suppresses tumor necrosis factor-\u03b1 and ameliorates murine intestinal inflammation. Inflamm. Bowel Dis. 20, 685\u2013694 (2014).","journal-title":"Inflamm. Bowel Dis."},{"key":"465_CR74","doi-asserted-by":"publisher","first-page":"e86842","DOI":"10.1371\/journal.pone.0086842","volume":"9","author":"MC Hunter","year":"2014","unstructured":"Hunter, M. C. et al. Hsp90 binds directly to fibronectin and inhibition reduces the extracellular fibronectin matrix in breast cancer cells. PLoS ONE 9, e86842 (2014).","journal-title":"PLoS ONE"},{"key":"465_CR75","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1042\/bj20030351","volume":"374","author":"M Okada","year":"2003","unstructured":"Okada, M., Itoh, H., Hatakeyama, T., Tokumitsu, H. & Kobayashi, R. Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and amlexanox. Biochem. J. 374, 433\u2013441 (2003).","journal-title":"Biochem. J."},{"key":"465_CR76","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1111\/j.1750-3639.2002.tb00462.x","volume":"12","author":"J van Horssen","year":"2002","unstructured":"van Horssen, J. et al. Collagen XVIII: A novel heparan sulfate proteoglycan associated with vascular amyloid depositions and senile plaques in Alzheimer\u2019s disease brains. Brain Pathol. 12, 456\u2013462 (2002).","journal-title":"Brain Pathol."},{"key":"465_CR77","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.brainres.2010.09.023","volume":"1360","author":"A Al Ahmad","year":"2010","unstructured":"Al Ahmad, A. et al. Endostatin binds nerve growth factor and thereby inhibits neurite outgrowth and neuronal migration in-vitro. Brain Res. 1360, 28\u201339 (2010).","journal-title":"Brain Res."},{"key":"465_CR78","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/modpathol.3800336","volume":"18","author":"T-H Hu","year":"2005","unstructured":"Hu, T.-H. et al. Increased endostatin\/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma. Mod. Pathol. 18, 663\u2013672 (2005).","journal-title":"Mod. Pathol."},{"key":"465_CR79","doi-asserted-by":"publisher","first-page":"22597","DOI":"10.1038\/srep22597","volume":"6","author":"Y Zhang","year":"2016","unstructured":"Zhang, Y. & Stefanovic, B. Akt mediated phosphorylation of LARP6; critical step in biosynthesis of type I collagen. Sci. Rep. 6, 22597 (2016).","journal-title":"Sci. Rep."},{"key":"465_CR80","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/path.5363","volume":"250","author":"KA Wegner","year":"2020","unstructured":"Wegner, K. A. et al. Prostate epithelial-specific expression of activated PI3K drives stromal collagen production and accumulation. J. Pathol. 250, 231\u2013242 (2020).","journal-title":"J. Pathol."},{"key":"465_CR81","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.humpath.2013.08.015","volume":"45","author":"W Chen","year":"2014","unstructured":"Chen, W., Rock, J. B., Yearsley, M. M., Ferrell, L. D. & Frankel, W. L. Different collagen types show distinct rates of increase from early to late stages of hepatitis C-related liver fibrosis. Hum. Pathol. 45, 160\u2013165 (2014).","journal-title":"Hum. Pathol."},{"key":"465_CR82","doi-asserted-by":"publisher","first-page":"20753","DOI":"10.1073\/pnas.2004281117","volume":"117","author":"LM Williams","year":"2020","unstructured":"Williams, L. M. et al. Identifying collagen VI as a target of fibrotic diseases regulated by CREBBP\/EP300. Proc. Natl. Acad. Sci. USA 117, 20753 (2020).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"465_CR83","doi-asserted-by":"publisher","first-page":"e57621","DOI":"10.1371\/journal.pone.0057621","volume":"8","author":"X-H Li","year":"2013","unstructured":"Li, X.-H. et al. Gene expression profile of the hippocampus of rats subjected to chronic immobilization stress. PLoS ONE 8, e57621 (2013).","journal-title":"PLoS ONE"},{"key":"465_CR84","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/1755-1536-4-21","volume":"4","author":"WS To","year":"2011","unstructured":"To, W. S. & Midwood, K. S. Plasma and cellular fibronectin: Distinct and independent functions during tissue repair. Fibrogenesis Tissue Repair 4, 21 (2011).","journal-title":"Fibrogenesis Tissue Repair"},{"key":"465_CR85","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00018-015-2050-8","volume":"73","author":"MMA Almutairi","year":"2016","unstructured":"Almutairi, M. M. A., Gong, C., Xu, Y. G., Chang, Y. & Shi, H. Factors controlling permeability of the blood-brain barrier. Cell Mol. Life Sci. 73, 57\u201377 (2016).","journal-title":"Cell Mol. Life Sci."},{"key":"465_CR86","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s12974-018-1238-x","volume":"15","author":"AH Sikkema","year":"2018","unstructured":"Sikkema, A. H. et al. Fibronectin aggregates promote features of a classically and alternatively activated phenotype in macrophages. J. Neuroinflam. 15, 218 (2018).","journal-title":"J. Neuroinflam."},{"key":"465_CR87","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1002\/hep.28704","volume":"64","author":"H Jones","year":"2016","unstructured":"Jones, H. et al. Inhibition of mast cell-secreted histamine decreases biliary proliferation and fibrosis in primary sclerosing cholangitis Mdr2\u2212\/\u2212 mice. Hepatology 64, 1202\u20131216 (2016).","journal-title":"Hepatology"},{"key":"465_CR88","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1038\/labinvest.2016.89","volume":"96","author":"L Hargrove","year":"2016","unstructured":"Hargrove, L. et al. Isolation and characterization of hepatic mast cells from cholestatic rats. Lab. Invest. 96, 1198\u20131210 (2016).","journal-title":"Lab. Invest."},{"key":"465_CR89","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/0092-8674(95)90184-1","volume":"83","author":"C Wu","year":"1995","unstructured":"Wu, C., Keivenst, V. M., O\u2019Toole, T. E., McDonald, J. A. & Ginsberg, M. H. Integrin activation and cytoskeletal interaction are essential for the assembly of a fibronectin matrix. Cell 83, 715\u2013724 (1995).","journal-title":"Cell"},{"key":"465_CR90","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1038\/labinvest.2015.82","volume":"95","author":"RL Stewart","year":"2015","unstructured":"Stewart, R. L. & O\u2019Connor, K. L. Clinical significance of the integrin \u03b16\u03b24 in human malignancies. Lab. Invest. 95, 976\u2013986 (2015).","journal-title":"Lab. Invest."},{"key":"465_CR91","doi-asserted-by":"publisher","first-page":"e139","DOI":"10.1038\/tp.2012.64","volume":"2","author":"M Sathyanesan","year":"2012","unstructured":"Sathyanesan, M. et al. A molecular characterization of the choroid plexus and stress-induced gene regulation. Transl. Psychiatry 2, e139 (2012).","journal-title":"Transl. Psychiatry"},{"key":"465_CR92","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12974-018-1204-7","volume":"15","author":"Y Yang","year":"2018","unstructured":"Yang, Y. et al. Inflammation leads to distinct populations of extracellular vesicles from microglia. J. Neuroinflam. 15, 168 (2018).","journal-title":"J. Neuroinflam."},{"key":"465_CR93","doi-asserted-by":"publisher","first-page":"22962","DOI":"10.1038\/srep22962","volume":"6","author":"JL Richens","year":"2016","unstructured":"Richens, J. L. et al. Rationalizing the role of Keratin 9 as a biomarker for Alzheimer\u2019s disease. Sci. Rep. 6, 22962 (2016).","journal-title":"Sci. Rep."},{"key":"465_CR94","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1369\/0022155418757443","volume":"66","author":"AM Marzeda","year":"2018","unstructured":"Marzeda, A. M. & Midwood, K. S. Internal affairs: Tenascin-C as a clinically relevant, endogenous driver of innate immunity. J. Histochem. Cytochem. 66, 289\u2013304 (2018).","journal-title":"J. Histochem. Cytochem."},{"key":"465_CR95","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1093\/jnen\/nlw062","volume":"75","author":"Z Mi","year":"2016","unstructured":"Mi, Z. et al. Tenascin-C is associated with cored amyloid-\u03b2 plaques in Alzheimer disease and pathology burdened cognitively normal elderly. J. Neuropathol. Exp. Neurol. 75, 868\u2013876 (2016).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"465_CR96","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.bbi.2019.06.047","volume":"81","author":"V Haage","year":"2019","unstructured":"Haage, V. et al. Tenascin C regulates multiple microglial functions involving TLR4 signaling and HDAC1. Brain Behav. Immunol. 81, 470\u2013483 (2019).","journal-title":"Brain Behav. Immunol."},{"key":"465_CR97","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1007\/s12035-016-9720-x","volume":"54","author":"H Dong","year":"2017","unstructured":"Dong, H. et al. Suppression of brain mast cells degranulation inhibits microglial activation and central nervous system inflammation. Mol. Neurobiol. 54, 997\u20131007 (2017).","journal-title":"Mol. Neurobiol."},{"key":"465_CR98","first-page":"782","volume":"5","author":"Y Nong","year":"2015","unstructured":"Nong, Y. et al. Tenascin-C expression is associated with poor prognosis in hepatocellular carcinoma (HCC) patients and the inflammatory cytokine TNF-\u03b1-induced TNC expression promotes migration in HCC cells. Am. J. Cancer Res. 5, 782\u2013791 (2015).","journal-title":"Am. J. Cancer Res."},{"key":"465_CR99","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1749-8104-4-26","volume":"4","author":"KM Kollins","year":"2009","unstructured":"Kollins, K. M., Bell, R. L., Butts, M. & Withers, G. S. Dendrites differ from axons in patterns of microtubule stability and polymerization during development. Neural Dev. 4, 26\u201326 (2009).","journal-title":"Neural Dev."},{"key":"465_CR100","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.conb.2018.03.001","volume":"51","author":"JH Park","year":"2018","unstructured":"Park, J. H. & Roll-Mecak, A. The tubulin code in neuronal polarity. Curr. Opin. Neurobiol. 51, 95\u2013102 (2018).","journal-title":"Curr. Opin. Neurobiol."},{"key":"465_CR101","doi-asserted-by":"publisher","first-page":"7853","DOI":"10.1073\/pnas.0409626102","volume":"102","author":"C Erck","year":"2005","unstructured":"Erck, C. et al. A vital role of tubulin-tyrosine-ligase for neuronal organization. Proc. Natl. Acad. Sci. USA 102, 7853 (2005).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"465_CR102","doi-asserted-by":"publisher","first-page":"14765","DOI":"10.1074\/jbc.M114.622753","volume":"290","author":"W Song","year":"2015","unstructured":"Song, W., Cho, Y., Watt, D. & Cavalli, V. Tubulin-tyrosine ligase (TTL)-mediated Increase in tyrosinated \u03b1-tubulin in injured axons is required for retrograde injury signaling and axon regeneration. J. Biol. Chem. 290, 14765\u201314775 (2015).","journal-title":"J. Biol. Chem."},{"key":"465_CR103","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1038\/s41467-017-01744-5","volume":"8","author":"H Ju Lee","year":"2017","unstructured":"Ju Lee, H. et al. A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat. Commun. 8, 1456 (2017).","journal-title":"Nat. Commun."},{"key":"465_CR104","doi-asserted-by":"publisher","first-page":"eaax2166","DOI":"10.1126\/sciadv.aax2166","volume":"5","author":"H Guo","year":"2019","unstructured":"Guo, H. et al. Disruptive variants of CSDE1 associate with autism and interfere with neuronal development and synaptic transmission. Sci. Adv. 5, eaax2166 (2019).","journal-title":"Sci. Adv."},{"key":"465_CR105","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.molcel.2017.12.020","volume":"69","author":"J-Y Youn","year":"2018","unstructured":"Youn, J.-Y. et al. High-density proximity mapping reveals the subcellular organization of mRNA-associated granules and bodies. Mol. Cell 69, 517-532.e11 (2018).","journal-title":"Mol. Cell"},{"key":"465_CR106","doi-asserted-by":"publisher","first-page":"G481","DOI":"10.1152\/ajpgi.00234.2009","volume":"298","author":"S Hu","year":"2010","unstructured":"Hu, S., Claud, E. C., Musch, M. W. & Chang, E. B. Stress granule formation mediates the inhibition of colonic Hsp70 translation by interferon-\u03b3 and tumor necrosis factor-\u03b1. Am. J. Physiol. Gastrointest. Liver Physiol. 298, G481\u2013G492 (2010).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"465_CR107","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41583-019-0222-5","volume":"20","author":"B Wolozin","year":"2019","unstructured":"Wolozin, B. & Ivanov, P. Stress granules and neurodegeneration. Nat. Rev. Neurosci. 20, 649\u2013666 (2019).","journal-title":"Nat. Rev. Neurosci."},{"key":"465_CR108","doi-asserted-by":"publisher","first-page":"e1000565","DOI":"10.1371\/journal.pbio.1000565","volume":"8","author":"V Kaltezioti","year":"2010","unstructured":"Kaltezioti, V. et al. Prox1 regulates the notch1-mediated inhibition of neurogenesis. PLoS Biol 8, e1000565 (2010).","journal-title":"PLoS Biol"},{"key":"465_CR109","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1161\/ATVBAHA.117.310388","volume":"38","author":"LC Poulsen","year":"2018","unstructured":"Poulsen, L. C. et al. Inhibition of endothelial NOTCH1 signaling attenuates inflammation by reducing cytokine-mediated histone acetylation at inflammatory enhancers. Arterioscl. Thromb. Vasc. Biol. 38, 854\u2013869 (2018).","journal-title":"Arterioscl. Thromb. Vasc. Biol."},{"key":"465_CR110","doi-asserted-by":"publisher","first-page":"e0145334","DOI":"10.1371\/journal.pone.0145334","volume":"10","author":"K Kato","year":"2016","unstructured":"Kato, K. et al. Prox1 inhibits proliferation and is required for differentiation of the oligodendrocyte cell lineage in the mouse. PLoS ONE 10, e0145334 (2016).","journal-title":"PLoS ONE"},{"key":"465_CR111","doi-asserted-by":"publisher","first-page":"3443","DOI":"10.1007\/s00018-020-03709-2","volume":"78","author":"V Kaltezioti","year":"2021","unstructured":"Kaltezioti, V. et al. Prox1 inhibits neurite outgrowth during central nervous system development. Cell. Mol. Life Sci. 78, 3443\u20133465 (2021).","journal-title":"Cell. Mol. Life Sci."},{"key":"465_CR112","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1126\/science.aaa4903","volume":"350","author":"DB Wheeler","year":"2015","unstructured":"Wheeler, D. B., Zoncu, R., Root, D. E., Sabatini, D. M. & Sawyers, C. L. Identification of an oncogenic RAB protein. Science 350, 211 (2015).","journal-title":"Science"},{"key":"465_CR113","first-page":"2424","volume":"126","author":"H Kobayashi","year":"2013","unstructured":"Kobayashi, H. & Fukuda, M. Rab35 establishes the EHD1-association site by coordinating two distinct effectors during neurite outgrowth. J. Cell Sci. 126, 2424\u20132435 (2013).","journal-title":"J. Cell Sci."},{"key":"465_CR114","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1242\/bio.20148771","volume":"3","author":"H Kobayashi","year":"2014","unstructured":"Kobayashi, H., Etoh, K., Ohbayashi, N. & Fukuda, M. Rab35 promotes the recruitment of Rab8, Rab13 and Rab36 to recycling endosomes through MICAL-L1 during neurite outgrowth. Biol. Open 3, 803\u2013814 (2014).","journal-title":"Biol. Open"},{"key":"465_CR115","doi-asserted-by":"publisher","first-page":"16803","DOI":"10.1038\/s41598-020-74013-z","volume":"10","author":"S Bhat","year":"2020","unstructured":"Bhat, S. et al. Rab35 and its effectors promote formation of tunneling nanotubes in neuronal cells. Sci. Rep. 10, 16803 (2020).","journal-title":"Sci. Rep."},{"key":"465_CR116","doi-asserted-by":"publisher","first-page":"14529","DOI":"10.1038\/s41598-019-50971-x","volume":"9","author":"S Goodman","year":"2019","unstructured":"Goodman, S., Naphade, S., Khan, M., Sharma, J. & Cherqui, S. Macrophage polarization impacts tunneling nanotube formation and intercellular organelle trafficking. Sci. Rep. 9, 14529 (2019).","journal-title":"Sci. Rep."},{"key":"465_CR117","doi-asserted-by":"publisher","first-page":"3030","DOI":"10.3389\/fimmu.2019.03030","volume":"10","author":"J Westman","year":"2020","unstructured":"Westman, J., Grinstein, S. & Marques, P. E. Phagocytosis of necrotic debris at sites of injury and inflammation. Front. Immunol. 10, 3030 (2020).","journal-title":"Front. Immunol."},{"key":"465_CR118","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/1742-2094-11-48","volume":"11","author":"D Doens","year":"2014","unstructured":"Doens, D. & Fern\u00e1ndez, P. L. Microglia receptors and their implications in the response to amyloid \u03b2 for Alzheimer\u2019s disease pathogenesis. J. Neuroinflam. 11, 48 (2014).","journal-title":"J. Neuroinflam."},{"key":"465_CR119","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.redox.2017.10.014","volume":"14","author":"C Cheignon","year":"2018","unstructured":"Cheignon, C. et al. Oxidative stress and the amyloid beta peptide in Alzheimer\u2019s disease. Redox Biol. 14, 450\u2013464 (2018).","journal-title":"Redox Biol."},{"key":"465_CR120","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/cdd.2013.180","volume":"21","author":"P Joshi","year":"2014","unstructured":"Joshi, P. et al. Microglia convert aggregated amyloid-\u03b2 into neurotoxic forms through the shedding of microvesicles. Cell Death Differ. 21, 582\u2013593 (2014).","journal-title":"Cell Death Differ."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00465-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00465-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00465-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T07:24:46Z","timestamp":1675841086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-00465-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,12]]},"references-count":120,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["465"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-00465-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-825684\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,12]]},"assertion":[{"value":"18 August 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Y.W. and M.A.D. are employed by AZTherapies, Inc. S.C. and T.M.S. declare no competing interests. D.R.E. is an Associate Professor at Harvard Medical School and holds a part time employee position at Massachusetts General Hospital and serves as Chairmen at AZTherapies, Inc.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22161"}}