{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:26:47Z","timestamp":1785166007132,"version":"3.55.0"},"reference-count":117,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glial cells, particularly astrocytes and microglia, are central to maintaining CNS homeostasis and coordinating responses to injury through tightly regulated metabolic, inflammatory, and mechanosensitive processes. Emerging evidence identifies the Hippo signaling pathway and its downstream effectors YAP\/TAZ as key regulators of glial functions, influencing proliferation, polarization, intercellular communication, and the balance between neuroprotection and neurotoxicity. This review discusses the Hippo signaling pathway and its transcriptional co-activators YAP\/TAZ as context-dependent hubs integrating mechanical, metabolic, and immune cues in astrocytes and microglia. Particular attention is given to MST1\/2- and YAP\/TAZ-dependent signaling in microglia, which governs inflammatory states, redox balance, mitophagy, and mechanosensing. In astrocytes, Hippo\u2013YAP signaling emerges as a bidirectional regulator of reactive gliosis and neuroprotection, capable of constraining excessive scar formation. However, when chronically suppressed, it impairs glutamate clearance, metabolic support, and resistance to neurodegeneration. Disruption of Hippo signaling in glial tumors is also considered, with YAP\/TAZ\u2013TEAD complexes driving glioblastoma stemness, infiltrative growth, immune evasion, and therapy resistance. Finally, therapeutic perspectives are outlined that emphasize context-selective modulation of Hippo signaling in the CNS. Overall, Hippo\u2013YAP\/TAZ signaling is presented as a highly context-dependent regulator at the interface of glial inflammation, neurodegeneration, and glioma biology and as a promising but demanding target for future CNS therapies.<\/jats:p>","DOI":"10.3390\/ijms27083672","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T14:53:23Z","timestamp":1776696803000},"page":"3672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hippo\u2013YAP\/TAZ Signaling in Astrocytes and Microglia: Role in Neuroinflammation, Neurodegeneration and Glial Tumors"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5411-3778","authenticated-orcid":false,"given":"Emilia","family":"Zgorzynska","sequence":"first","affiliation":[{"name":"Department of Cell-to-Cell Communication, Medical University of Lodz, Mazowiecka 6\/8, 92-215 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00401-009-0619-8","article-title":"Astrocytes: Biology and Pathology","volume":"119","author":"Sofroniew","year":"2010","journal-title":"Acta Neuropathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.tins.2020.01.003","article-title":"Astrocytes and Microglia: In Sickness and in Health","volume":"43","author":"Vainchtein","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s11064-014-1403-2","article-title":"Why Are Astrocytes Important?","volume":"40","author":"Verkhratsky","year":"2015","journal-title":"Neurochem. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/s41593-020-00783-4","article-title":"Reactive Astrocyte Nomenclature, Definitions, and Future Directions","volume":"24","author":"Escartin","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev-neuro-112723-031738","article-title":"Heterogeneity of Astrocyte Reactivity","volume":"48","author":"Clayton","year":"2025","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Huang, Y., Cao, Y., and Yang, J. (2024). Astrocyte-Mediated Neuroinflammation in Neurological Conditions. Biomolecules, 14.","DOI":"10.3390\/biom14101204"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/nrn3898","article-title":"Astrocyte Barriers to Neurotoxic Inflammation","volume":"16","author":"Sofroniew","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lauro, C., and Limatola, C. (2020). Metabolic Reprograming of Microglia in the Regulation of the Innate Inflammatory Response. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00493"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"M\u00fcller, L., Di Benedetto, S., and M\u00fcller, V. (2025). The Dual Nature of Neuroinflammation in Networked Brain. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1659947"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yang, G., Xu, X., Gao, W., Wang, X., Zhao, Y., and Xu, Y. (2025). Microglia-Orchestrated Neuroinflammation and Synaptic Remodeling: Roles of pro-Inflammatory Cytokines and Receptors in Neurodegeneration. Front. Cell Neurosci., 19.","DOI":"10.3389\/fncel.2025.1700692"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s12974-021-02355-0","article-title":"Microglia and Astrocyte Involvement in Neurodegeneration and Brain Cancer","volume":"18","author":"Vandenbark","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Matejuk, A., and Ransohoff, R.M. (2020). Crosstalk Between Astrocytes and Microglia: An Overview. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.01416"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/s41593-020-0597-7","article-title":"Microglia and Macrophages Promote Corralling, Wound Compaction and Recovery after Spinal Cord Injury via Plexin-B2","volume":"23","author":"Zhou","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.7150\/thno.48761","article-title":"M2 Microglial Small Extracellular Vesicles Reduce Glial Scar Formation via the MiR-124\/STAT3 Pathway after Ischemic Stroke in Mice","volume":"11","author":"Li","year":"2021","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41467-019-08446-0","article-title":"Microglia Are an Essential Component of the Neuroprotective Scar That Forms after Spinal Cord Injury","volume":"10","author":"Bretheau","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41586-018-0119-x","article-title":"Microglial Control of Astrocytes in Response to Microbial Metabolites","volume":"557","author":"Rothhammer","year":"2018","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"eabf1230","DOI":"10.1126\/science.abf1230","article-title":"Barcoded Viral Tracing of Single-Cell Interactions in Central Nervous System Inflammation","volume":"372","author":"Clark","year":"2021","journal-title":"Science"},{"key":"ref_18","first-page":"22538","article-title":"Inflammatory Factors and Amyloid \u03b2-Induced Microglial Polarization Promote Inflammatory Crosstalk with Astrocytes","volume":"12","author":"Xie","year":"2020","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","article-title":"Microglia in Neurodegenerative Diseases: Mechanism and Potential Therapeutic Targets","volume":"8","author":"Gao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.2174\/1570159X21666221129121715","article-title":"Bidirectional Communication Between Microglia and Astrocytes in Neuroinflammation","volume":"21","author":"Bhusal","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e98697","DOI":"10.15252\/embj.201798697","article-title":"NF-\u039aB Activation in Astrocytes Drives a Stage-Specific Beneficial Neuroimmunological Response in ALS","volume":"37","author":"Schurr","year":"2018","journal-title":"EMBO J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/s41586-021-03734-6","article-title":"Astrocytic Interleukin-3 Programs Microglia and Limits Alzheimer\u2019s Disease","volume":"595","author":"McAlpine","year":"2021","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e51696","DOI":"10.15252\/embr.202051696","article-title":"SFRP1 Modulates Astrocyte-to-Microglia Crosstalk in Acute and Chronic Neuroinflammation","volume":"22","author":"Pereyra","year":"2021","journal-title":"EMBO Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12974-020-02059-x","article-title":"Microglial Inflammation after Chronic Spinal Cord Injury Is Enhanced by Reactive Astrocytes via the Fibronectin\/\u03921 Integrin Pathway","volume":"18","author":"Yoshizaki","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"112550","DOI":"10.1016\/j.fct.2021.112550","article-title":"Reactive Astrocytes Induced by 2-Chloroethanol Modulate Microglia Polarization through IL-1\u03b2, TNF-\u03b1, and INOS Upregulation","volume":"157","author":"Wang","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eaar2124","DOI":"10.1126\/scisignal.aar2124","article-title":"Glutathione S-Transferases Promote Proinflammatory Astrocyte-Microglia Communication during Brain Inflammation","volume":"12","author":"Kano","year":"2019","journal-title":"Sci. Signal"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s12264-024-01308-w","article-title":"YAP Signaling in Glia: Pivotal Roles in Neurological Development, Regeneration and Diseases","volume":"41","author":"Lin","year":"2025","journal-title":"Neurosci. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/S0092-8674(03)00557-9","article-title":"The Drosophila Mst Ortholog, Hippo, Restricts Growth and Cell Proliferation and Promotes Apoptosis","volume":"114","author":"Harvey","year":"2003","journal-title":"Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11760","DOI":"10.1074\/jbc.M211085200","article-title":"Regulation of Mammalian STE20-like Kinase 2 (MST2) by Protein Phosphorylation\/Dephosphorylation and Proteolysis","volume":"278","author":"Deng","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.bbrc.2006.03.244","article-title":"The Human Tumour Suppressor LATS1 Is Activated by Human MOB1 at the Membrane","volume":"345","author":"Hergovich","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1038\/sj.onc.1208445","article-title":"The Ste20-like Kinase Mst2 Activates the Human Large Tumor Suppressor Kinase Lats1","volume":"24","author":"Chan","year":"2005","journal-title":"Oncogene"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8357","DOI":"10.1038\/ncomms9357","article-title":"MAP4K Family Kinases Act in Parallel to MST1\/2 to Activate LATS1\/2 in the Hippo Pathway","volume":"6","author":"Meng","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.devcel.2015.08.014","article-title":"Identification of Happyhour\/MAP4K as Alternative Hpo\/Mst-like Kinases in the Hippo Kinase Cascade","volume":"34","author":"Zheng","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/j.molcel.2016.10.034","article-title":"Characterization of Hippo Pathway Components by Gene Inactivation","volume":"64","author":"Plouffe","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7018","DOI":"10.1074\/jbc.C110.212621","article-title":"Hippo Pathway-Independent Restriction of TAZ and YAP by Angiomotin","volume":"286","author":"Chan","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"dev196675","DOI":"10.1242\/dev.196675","article-title":"TEAD Family Transcription Factors in Development and Disease","volume":"148","author":"Currey","year":"2021","journal-title":"Development"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Masliantsev, K., Karayan-tapon, L., and Guichet, P.O. (2021). Hippo Signaling Pathway in Gliomas. Cells, 10.","DOI":"10.3390\/cells10010184"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e12762","DOI":"10.1111\/nan.12762","article-title":"Emerging Roles for the YAP\/TAZ Transcriptional Regulators in Brain Tumour Pathology and Targeting Options","volume":"48","author":"Strepkos","year":"2022","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/emboj.2011.487","article-title":"A Molecular Mechanism That Links Hippo Signalling to the Inhibition of Wnt\/\u03b2-Catenin Signalling","volume":"31","author":"Imajo","year":"2012","journal-title":"EMBO J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cell.2014.06.013","article-title":"YAP\/TAZ Incorporation in the \u03b2-Catenin Destruction Complex Orchestrates the Wnt Response","volume":"158","author":"Azzolin","year":"2014","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"11730","DOI":"10.1074\/jbc.M111.327767","article-title":"Wnt\/\u03b2-Catenin Signaling Regulates Yes-Associated Protein (YAP) Gene Expression in Colorectal Carcinoma Cells","volume":"287","author":"Konsavage","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1016\/j.cell.2015.07.013","article-title":"Alternative Wnt Signaling Activates YAP\/TAZ","volume":"162","author":"Park","year":"2015","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1002\/glia.24332","article-title":"Yes-Associated Protein Regulates Glutamate Homeostasis through Promoting the Expression of Excitatory Amino Acid Transporter-2 in Astrocytes via \u03b2-Catenin Signaling","volume":"71","author":"Xu","year":"2023","journal-title":"Glia"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Aghaizu, N.D., Jin, H., and Whiting, P.J. (2020). Dysregulated Wnt Signalling in the Alzheimer\u2019s Brain. Brain Sci., 10.","DOI":"10.3390\/brainsci10120902"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1084\/jem.20111653","article-title":"TGF-\u03b2 Synergizes with Defects in the Hippo Pathway to Stimulate Human Malignant Mesothelioma Growth","volume":"209","author":"Fujii","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.molcel.2016.05.012","article-title":"TGF-\u03b2 Targets the Hippo Pathway Scaffold RASSF1A to Facilitate YAP\/SMAD2 Nuclear Translocation","volume":"63","author":"Pefani","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8480","DOI":"10.7150\/thno.60031","article-title":"Astrocytic YAP Protects the Optic Nerve and Retina in an Experimental Autoimmune Encephalomyelitis Model through TGF-\u03b2 Signaling","volume":"11","author":"Wu","year":"2021","journal-title":"Theranostics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e202101010","DOI":"10.26508\/lsa.202101010","article-title":"Hierarchy of TGF\u03b2\/SMAD, Hippo\/YAP\/TAZ, and Wnt\/\u03b2-Catenin Signaling in Melanoma Phenotype Switching","volume":"5","author":"Pirkl","year":"2022","journal-title":"Life Sci. Alliance"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ydbio.2012.06.014","article-title":"Akt Is Negatively Regulated by Hippo Signaling for Growth Inhibition in Drosophila","volume":"369","author":"Ye","year":"2012","journal-title":"Dev. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Borreguero-Mu\u00f1oz, N., Fletcher, G.C., Aguilar-Aragon, M., Elbediwy, A., Vincent-Mistiaen, Z.I., and Thompson, B.J. (2019). The Hippo Pathway Integrates PI3K-Akt Signals with Mechanical and Polarity Cues to Control Tissue Growth. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000509"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"209","DOI":"10.5483\/BMBRep.2018.51.5.095","article-title":"Insulin Receptor Substrate 2: A Bridge between Hippo and AKT Pathways","volume":"51","author":"Jeong","year":"2018","journal-title":"BMB Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"493","DOI":"10.4196\/kjpp.2023.27.5.493","article-title":"Inhibition of the Interaction between Hippo\/YAP and Akt Signaling with Ursolic Acid and 3\u20323-Diindolylmethane Suppresses Esophageal Cancer Tumorigenesis","volume":"27","author":"Meng","year":"2023","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.1038\/s41467-018-07022-2","article-title":"Reciprocal Inhibition of YAP\/TAZ and NF-\u039aB Regulates Osteoarthritic Cartilage Degradation","volume":"9","author":"Deng","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e2115316119","DOI":"10.1073\/pnas.2115316119","article-title":"HTLV-1 Activates YAP via NF-\u039aB\/P65 to Promote Oncogenesis","volume":"119","author":"Zhao","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Wang, S., Zhou, L., Ling, L., Meng, X., Chu, F., Zhang, S., and Zhou, F. (2020). The Crosstalk Between Hippo-YAP Pathway and Innate Immunity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00323"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1002\/jat.4065","article-title":"Role of the Hippo-YAP\/NF-\u039aB Signaling Pathway Crosstalk in Regulating Biological Behaviors of Macrophages under Titanium Ion Exposure","volume":"41","author":"Tang","year":"2021","journal-title":"J. Appl. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"108430","DOI":"10.1016\/j.jbc.2025.108430","article-title":"The Hippo Pathway Effector YAP Inhibits NF-\u039aB Signaling and CcRCC Growth by Opposing ZHX2","volume":"301","author":"Li","year":"2025","journal-title":"J. Biol. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"109983","DOI":"10.1016\/j.isci.2024.109983","article-title":"Hippo-PKC\u03b6-NF\u03baB Signaling Axis: A Druggable Modulator of Chondrocyte Responses to Mechanical Stress","volume":"27","author":"Cai","year":"2024","journal-title":"iScience"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1002\/jcp.29070","article-title":"Proinflammation Effect of Mst1 Promotes BV-2 Cell Death via Augmenting Drp1-Mediated Mitochondrial Fragmentation and Activating the JNK Pathway","volume":"235","author":"Tian","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1080\/01616412.2016.1174423","article-title":"Malibatol A Enhances Alternative Activation of Microglia by Inhibiting Phosphorylation of Mammalian Ste20-like Kinase1 in OGD-BV-2 Cells","volume":"38","author":"Weng","year":"2016","journal-title":"Neurol. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.7150\/ijbs.87057","article-title":"Inactivation of MST1\/2 Controls Macrophage Polarization to Affect Macrophage-Related Disease via YAP and Non-YAP Mechanisms","volume":"20","author":"An","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.omtn.2022.03.025","article-title":"TAZ Ameliorates the Microglia-Mediated Inflammatory Response via the Nrf2-ROS-NF-\u039aB Pathway","volume":"28","author":"Huang","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s11658-018-0081-5","article-title":"Mitochonic Acid 5 Activates the MAPK\u2013ERK\u2013Yap Signaling Pathways to Protect Mouse Microglial BV-2 Cells against TNF\u03b1-Induced Apoptosis via Increased Bnip3-Related Mitophagy","volume":"23","author":"Lei","year":"2018","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Fazendeiro, B., Machado, I., Rolo, A., Rodrigues Santos, P., Ambr\u00f3sio, A.F., Santos, P.F., and L\u00e9ger, H. (2025). NDR2 Kinase Regulates Microglial Metabolic Adaptation and Inflammatory Response: Critical Role in Glucose-Dependent Functional Plasticity. Int. J. Mol. Sci., 26.","DOI":"10.1101\/2025.06.12.659313"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12974-026-03732-3","article-title":"MST1 Promotes Microglial Pyroptosis and Neuroinflammation in Alzheimer\u2019s Disease by Regulating the Novel DPP8\/NLRP1\/Caspase-1\/GSDMD-N Axis","volume":"23","author":"Cui","year":"2026","journal-title":"J. Neuroinflammation"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ayazi, M., Zivkovic, S., Hammel, G., Stefanovic, B., and Ren, Y. (2022). Fibrotic Scar in CNS Injuries: From the Cellular Origins of Fibroblasts to the Molecular Processes of Fibrotic Scar Formation. Cells, 11.","DOI":"10.3390\/cells11152371"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"557","DOI":"10.4103\/NRR.NRR-D-23-01130","article-title":"Mutual Regulation of Microglia and Astrocytes after Gas6 Inhibits Spinal Cord Injury","volume":"20","author":"Chen","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Hu, X., Huang, J., Li, Y., Dong, L., Chen, Y., Ouyang, F., Li, J., Li, Z., Jing, J., and Cheng, L. (2022). TAZ Induces Migration of Microglia and Promotes Neurological Recovery After Spinal Cord Injury. Front. Pharmacol., 13, Correction in Front. Pharmacol. 2022, 13, 995767.","DOI":"10.3389\/fphar.2022.995767"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1007\/s00018-021-03817-7","article-title":"Kindlin3 Regulates Biophysical Properties and Mechanics of Membrane to Cortex Attachment","volume":"78","author":"Dudiki","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e70061","DOI":"10.1002\/cbf.70061","article-title":"Matrix Stiffness Regulates Interleukin-10 Secretion in Human Microglia (HMC3) via YAP-Mediated Mechanotransduction","volume":"43","author":"Fang","year":"2025","journal-title":"Cell Biochem. Funct."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1111\/cns.14170","article-title":"Inhibition of TANK-Binding Kinase1 Attenuates the Astrocyte-Mediated Neuroinflammatory Response through YAP Signaling after Spinal Cord Injury","volume":"29","author":"Zhang","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Feng, S., Liu, L., Cheng, Y., Zhou, M., Zhu, H., Zhao, X., Chen, Z., Kan, S., Fu, X., and Hu, W. (2024). Icariin Promotes Functional Recovery in Rats after Spinal Cord Injury by Inhibiting YAP and Regulating PPM1B Ubiquitination to Inhibiting the Activation of Reactive Astrocytes. Front. Pharmacol., 15, Correction in Front. Pharmacol. 2024, 15, 1523605.","DOI":"10.3389\/fphar.2024.1434652"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1080\/01616412.2024.2359263","article-title":"MiR-540-3p Partially Recovers the Locomotor Function of Spinal Cord Injury Mice by Targeting SIX4\/Yap1 and Inactivation of Astrocytes","volume":"46","author":"Wang","year":"2024","journal-title":"Neurol. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"110276","DOI":"10.1016\/j.intimp.2023.110276","article-title":"Aging and TNF Induce Premature Senescence of Astrocytes after Spinal Cord Injury via Regulating YAP Expression","volume":"120","author":"Lin","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41419-025-07806-7","article-title":"Astrocytic YAP Prevents the Glutamate Neurotoxicity by Upregulation of EAAT2 Expression and Promotes the Gain of Stemness in Astrocytes in Ischemic Stroke Mice","volume":"16","author":"Luo","year":"2025","journal-title":"Cell Death Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"8176","DOI":"10.7150\/thno.113599","article-title":"An Unrecognized Mechanism of Self-Protection in Degenerating Neurons Mediated by Astrocytic YAP through Wnts\/\u03b2-Catenin\/EAAT2 Signaling in C9orf72-Poly-GA Mice","volume":"15","author":"Li","year":"2025","journal-title":"Theranostics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1093\/cercor\/bhv292","article-title":"YAP Is a Critical Inducer of SOCS3, Preventing Reactive Astrogliosis","volume":"26","author":"Huang","year":"2016","journal-title":"Cereb. Cortex"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Sobral, A.F., Costa, I., Teixeira, V., Silva, R., and Barbosa, D.J. (2025). Molecular Motors in Blood\u2013Brain Barrier Maintenance by Astrocytes. Brain Sci., 15.","DOI":"10.3390\/brainsci15030279"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41427-021-00304-0","article-title":"Matrix Stiffness Changes Affect Astrocyte Phenotype in an in Vitro Injury Model","volume":"13","author":"Hu","year":"2021","journal-title":"NPG Asia Mater."},{"key":"ref_80","first-page":"607","article-title":"ECM Stiffness Governs Endothelial Barrier Integrity through YAP-Mediated Stabilization of ZO-1","volume":"56","author":"Chi","year":"2026","journal-title":"Bioact. Mater."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"116703","DOI":"10.1016\/j.biopha.2024.116703","article-title":"YAP in Development and Disease: Navigating the Regulatory Landscape from Retina to Brain","volume":"175","author":"Zhao","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e70329","DOI":"10.1002\/mco2.70329","article-title":"Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets","volume":"6","author":"Mao","year":"2025","journal-title":"MedComm"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e13465","DOI":"10.1111\/acel.13465","article-title":"YAP Prevents Premature Senescence of Astrocytes and Cognitive Decline of Alzheimer\u2019s Disease through Regulating CDK6 Signaling","volume":"20","author":"Xu","year":"2021","journal-title":"Aging Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1101\/gad.176800.111","article-title":"The Transcriptional Coactivator TAZ Regulates Mesenchymal Differentiation in Malignant Glioma","volume":"25","author":"Bhat","year":"2011","journal-title":"Genes Dev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.jmoldx.2019.03.007","article-title":"Promoter Hypermethylation of Genes Encoding for RASSF\/Hippo Pathway Members Reveals Specific Alteration Pattern in Diffuse Gliomas","volume":"21","author":"Levallet","year":"2019","journal-title":"J. Mol. Diagn."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.biopha.2017.07.081","article-title":"TGF-\u03b2-Mediated Repression of MST1 by DNMT1 Promotes Glioma Malignancy","volume":"94","author":"Guo","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"117","DOI":"10.31083\/j.jin.2019.02.122","article-title":"MST1 Suppresses Viability and Promotes Apoptosis of Glioma Cells via Upregulating SIRT6 Expression","volume":"18","author":"Zhu","year":"2019","journal-title":"J. Integr. Neurosci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1158\/1535-7163.MCT-24-0594","article-title":"Moxidectin Unravels the Role of the Hippo\u2013YAP Pathway in Maintaining Immunity of Glioblastoma Multiforme","volume":"24","author":"Kaushik","year":"2025","journal-title":"Mol. Cancer Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ydbio.2020.12.018","article-title":"YAP1 and Its Fusion Proteins in Cancer Initiation, Progression and Therapeutic Resistance","volume":"475","author":"Szulzewsky","year":"2021","journal-title":"Dev. Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1097\/CM9.0000000000003679","article-title":"P4HA1 Mediates YAP Hydroxylation and Accelerates Collagen Synthesis in Temozolomide-Resistant Glioblastoma","volume":"138","author":"Li","year":"2025","journal-title":"Chin. Med. J."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.1007\/s11010-025-05250-x","article-title":"LncRNA BDNF-AS Binds to DNMT1 to Suppress Angiogenesis in Glioma by Promoting NEDD4L-Mediated YAP1 Ubiquitination","volume":"480","author":"Deng","year":"2025","journal-title":"Mol. Cell Biochem."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e70021","DOI":"10.1111\/bpa.70021","article-title":"Hippo Pathway Effectors Are Associated with Glioma Patient Survival, Control Cell Proliferation and Sterol Metabolism through TEAD3","volume":"35","author":"Masliantsev","year":"2025","journal-title":"Brain Pathol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s11060-014-1654-4","article-title":"Mst1 Regulates Glioma Cell Proliferation via the AKT\/MTOR Signaling Pathway","volume":"121","author":"Chao","year":"2015","journal-title":"J. Neurooncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s12031-019-1262-z","article-title":"LATS2 Inhibits Malignant Behaviors of Glioma Cells via Inactivating YAP","volume":"68","author":"Shi","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Wei, R., Zhou, J., Bui, B., and Liu, X. (2024). Glioma Actively Orchestrate a Self-Advantageous Extracellular Matrix to Promote Recurrence and Progression. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12751-3"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1038\/ncb3429","article-title":"Tissue Mechanics Promote IDH1-Dependent HIF1\u03b1-Tenascin C Feedback to Regulate Glioblastoma Aggression","volume":"18","author":"Miroshnikova","year":"2016","journal-title":"Nat. Cell Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10137","article-title":"Role of YAP\/TAZ in Mechanotransduction","volume":"474","author":"Dupont","year":"2011","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/s42003-021-01667-4","article-title":"Plexin-B2 Facilitates Glioblastoma Infiltration by Modulating Cell Biomechanics","volume":"4","author":"Huang","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s43018-020-00150-z","article-title":"Single-Cell Analyses Reveal YAP\/TAZ as Regulators of Stemness and Cell Plasticity in Glioblastoma","volume":"2","author":"Castellan","year":"2021","journal-title":"Nat. cancer"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4973","DOI":"10.1158\/0008-5472.CAN-17-0388","article-title":"Transglutaminase 2 Inhibition Reverses Mesenchymal Transdifferentiation of Glioma Stem Cells by Regulating C\/EBP\u03b2 Signaling","volume":"77","author":"Yin","year":"2017","journal-title":"Cancer Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"70080","DOI":"10.18632\/oncotarget.12148","article-title":"FRMD6 Inhibits Human Glioblastoma Growth and Progression by Negatively Regulating Activity of Receptor Tyrosine Kinases","volume":"7","author":"Xu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e195385","DOI":"10.1172\/jci.insight.195385","article-title":"Methylation-Induced Suppression of YAP\/TAZ Confers Sensitivity to HDAC Inhibitors in High-Grade IDH Mutant Gliomas","volume":"10","author":"Sears","year":"2025","journal-title":"JCI Insight"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7602","DOI":"10.1038\/s41598-017-07632-8","article-title":"Verteporfin Inhibits Growth of Human Glioma in Vitro without Light Activation","volume":"7","author":"Brodowska","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1093\/neuonc\/noab244","article-title":"Anti-Invasive Efficacy and Survival Benefit of the YAP-TEAD Inhibitor Verteporfin in Preclinical Glioblastoma Models","volume":"24","author":"Barrette","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.1021\/acs.jmedchem.2c01548","article-title":"Structure-Based Design of Y-Shaped Covalent TEAD Inhibitors","volume":"66","author":"Lu","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"e18330","DOI":"10.1111\/jcmm.18330","article-title":"YAP\/TAZ-TEAD Signalling Axis: A New Therapeutic Target in Malignant Pleural Mesothelioma","volume":"28","author":"Papavassiliou","year":"2024","journal-title":"J. Cell Mol. Med."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Battina, R., Rahhal, R., Wellstein, A., Riegel, A.T., and Sharif, G.M. (2025). Targeting TEAD in Cancer. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1692512"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6744","DOI":"10.1038\/s41467-022-34559-0","article-title":"Pharmacological Blockade of TEAD\u2013YAP Reveals Its Therapeutic Limitation in Cancer Cells","volume":"13","author":"Sun","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.ccr.2014.01.010","article-title":"A Peptide Mimicking VGLL4 Function Acts as a YAP Antagonist Therapy against Gastric Cancer","volume":"25","author":"Jiao","year":"2014","journal-title":"Cancer Cell"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3679","DOI":"10.1038\/s41598-025-30686-y","article-title":"The Impact of Inhibiting the Hippo Signaling Pathway Effector Molecule YAP1 on in Vitro Glioblastoma and Glioblastoma Stem Cells","volume":"16","author":"Ozates","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3944","DOI":"10.1038\/s44319-024-00217-3","article-title":"Identification of Resistance Mechanisms to Small-Molecule Inhibition of TEAD-Regulated Transcription","volume":"25","author":"Kulkarni","year":"2024","journal-title":"EMBO Rep."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"114576","DOI":"10.18632\/oncotarget.23051","article-title":"YAP Regulates PD-L1 Expression in Human NSCLC Cells","volume":"8","author":"Miao","year":"2017","journal-title":"Oncotarget"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.bbrc.2017.07.007","article-title":"Hippo Effector YAP Directly Regulates the Expression of PD-L1 Transcripts in EGFR-TKI-Resistant Lung Adenocarcinoma","volume":"491","author":"Lee","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"117677","DOI":"10.1016\/j.bcp.2026.117677","article-title":"Targeting the FBXW7-AKAP13-YAP Axis Suppresses Gliomagenesis by Dual Inhibition of Tumor Invasion and Macrophage Recruitment","volume":"246","author":"Zhang","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/s12951-023-01798-2","article-title":"BBB-on-a-Chip with Integrated Micro-TEER for Permeability Evaluation of Multi-Functionalized Gold Nanorods against Alzheimer\u2019s Disease","volume":"21","author":"Kogan","year":"2023","journal-title":"J. Nanobiotechnology"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1186\/s12967-024-05852-x","article-title":"MST1, a Novel Therapeutic Target for Alzheimer\u2019s Disease, Regulates Mitochondrial Homeostasis by Mediating Mitochondrial DNA Transcription and the PI3K-Akt-ROS Pathway","volume":"22","author":"Cui","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/s41467-020-14353-6","article-title":"YAP-Dependent Necrosis Occurs in Early Stages of Alzheimer\u2019s Disease and Regulates Mouse Model Pathology","volume":"11","author":"Tanaka","year":"2020","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3672\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T04:15:38Z","timestamp":1777090538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/8\/3672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":117,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["ijms27083672"],"URL":"https:\/\/doi.org\/10.3390\/ijms27083672","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}