{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:12:15Z","timestamp":1778314335574,"version":"3.51.4"},"reference-count":75,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070969"],"award-info":[{"award-number":["32070969"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["0127\/2019\/A3"],"award-info":[{"award-number":["0127\/2019\/A3"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["0113\/2018\/A3"],"award-info":[{"award-number":["0113\/2018\/A3"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["0038\/2020\/AMJ"],"award-info":[{"award-number":["0038\/2020\/AMJ"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["MYRG2018-00134-FHS"],"award-info":[{"award-number":["MYRG2018-00134-FHS"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["MYRG2020-00158-FSH"],"award-info":[{"award-number":["MYRG2020-00158-FSH"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Science and Technology Development Fund, Macau SAR","award":["32070969"],"award-info":[{"award-number":["32070969"]}]},{"name":"The Science and Technology Development Fund, Macau SAR","award":["0127\/2019\/A3"],"award-info":[{"award-number":["0127\/2019\/A3"]}]},{"name":"The Science and Technology Development Fund, Macau SAR","award":["0113\/2018\/A3"],"award-info":[{"award-number":["0113\/2018\/A3"]}]},{"name":"The Science and Technology Development Fund, Macau SAR","award":["0038\/2020\/AMJ"],"award-info":[{"award-number":["0038\/2020\/AMJ"]}]},{"name":"The Science and Technology Development Fund, Macau SAR","award":["MYRG2018-00134-FHS"],"award-info":[{"award-number":["MYRG2018-00134-FHS"]}]},{"name":"The Science and Technology Development Fund, Macau SAR","award":["MYRG2020-00158-FSH"],"award-info":[{"award-number":["MYRG2020-00158-FSH"]}]},{"name":"The Guangdong Provincial Funding Committee for Basic and Applied Fundamental Research (2022-Natural Science Foundation)","award":["32070969"],"award-info":[{"award-number":["32070969"]}]},{"name":"The Guangdong Provincial Funding Committee for Basic and Applied Fundamental Research (2022-Natural Science Foundation)","award":["0127\/2019\/A3"],"award-info":[{"award-number":["0127\/2019\/A3"]}]},{"name":"The Guangdong Provincial Funding Committee for Basic and Applied Fundamental Research (2022-Natural Science Foundation)","award":["0113\/2018\/A3"],"award-info":[{"award-number":["0113\/2018\/A3"]}]},{"name":"The Guangdong Provincial Funding Committee for Basic and Applied Fundamental Research (2022-Natural Science Foundation)","award":["0038\/2020\/AMJ"],"award-info":[{"award-number":["0038\/2020\/AMJ"]}]},{"name":"The Guangdong Provincial Funding Committee for Basic and Applied Fundamental Research (2022-Natural Science Foundation)","award":["MYRG2018-00134-FHS"],"award-info":[{"award-number":["MYRG2018-00134-FHS"]}]},{"name":"The Guangdong Provincial Funding Committee for Basic and Applied Fundamental Research (2022-Natural Science Foundation)","award":["MYRG2020-00158-FSH"],"award-info":[{"award-number":["MYRG2020-00158-FSH"]}]},{"name":"University of Macau","award":["32070969"],"award-info":[{"award-number":["32070969"]}]},{"name":"University of Macau","award":["0127\/2019\/A3"],"award-info":[{"award-number":["0127\/2019\/A3"]}]},{"name":"University of Macau","award":["0113\/2018\/A3"],"award-info":[{"award-number":["0113\/2018\/A3"]}]},{"name":"University of Macau","award":["0038\/2020\/AMJ"],"award-info":[{"award-number":["0038\/2020\/AMJ"]}]},{"name":"University of Macau","award":["MYRG2018-00134-FHS"],"award-info":[{"award-number":["MYRG2018-00134-FHS"]}]},{"name":"University of Macau","award":["MYRG2020-00158-FSH"],"award-info":[{"award-number":["MYRG2020-00158-FSH"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) is a chronic neurodegenerative disease characterized by the occurrence of cognitive deficits. With no effective treatments available, the search for new effective therapies has become a major focus of interest. In the present study, we describe the potential therapeutic effect of Artemisia annua (A. annua) extract on AD. Nine-month-old female 3xTg AD mice were treated with A. annua extract for three months via oral administration. Animals assigned to WT and model groups were administrated with an equal volume of water for the same period. Treated AD mice significantly improved the cognitive deficits and exhibited reduced A\u03b2 accumulation, hyper-phosphorylation of tau, inflammatory factor release and apoptosis when compared with untreated AD mice. Moreover, A. annua extract promoted the survival and proliferation of neural progenitor cells (NPS) and increased the expression of synaptic proteins. Further assessment of the implicated mechanisms revealed that A. annua extract regulates the YAP signaling pathway in 3xTg AD mice. Further studies comprised the incubation of PC12 cells with A\u03b21\u201342 at a concentration of 8 \u03bcM with or without different concentrations of A. annua extract for 24 h. Obtained ROS levels, mitochondrial membrane potential, caspase-3 activity, neuronal cell apoptosis and assessment of the signaling pathways involved was performed using western blot and immunofluorescence staining. The obtained results showed that A. annua extract significantly reversed the A\u03b21\u201342-induced increase in ROS levels, caspase-3 activity and neuronal cell apoptosis in vitro. Moreover, either inhibition of the YAP signaling pathway, using a specific inhibitor or CRISPR cas9 knockout of YAP gene, reduced the neuroprotective effect of the A. annua extract. These findings suggest that A. annua extract may be a new multi-target anti-AD drug with potential use in the prevention and treatment of AD.<\/jats:p>","DOI":"10.3390\/ijms24065259","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T02:30:33Z","timestamp":1678415433000},"page":"5259","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Artemisia annua Extract Improves the Cognitive Deficits and Reverses the Pathological Changes of Alzheimer\u2019s Disease via Regulating YAP Signaling"],"prefix":"10.3390","volume":"24","author":[{"given":"Wenshu","family":"Zhou","sequence":"first","affiliation":[{"name":"Center of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"}]},{"given":"Bingxi","family":"Lei","sequence":"additional","affiliation":[{"name":"Center of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"}]},{"given":"Chao","family":"Yang","sequence":"additional","affiliation":[{"name":"Center of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"}]},{"given":"Marta","family":"Silva","sequence":"additional","affiliation":[{"name":"Center of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"}]},{"given":"Xingan","family":"Xing","sequence":"additional","affiliation":[{"name":"Center of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"}]},{"given":"Hua","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR 999078, China"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-125X","authenticated-orcid":false,"given":"Jiahong","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR 999078, China"}]},{"given":"Wenhua","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center of Reproduction, Development & Aging and Institute of Translation Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China"},{"name":"Zhuhai UM Science & Technology Research Institute, Zhuhai 519000, China"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pardo-Moreno, T., Gonz\u00e1lez-Acedo, A., Rivas-Dom\u00ednguez, A., Garc\u00eda-Morales, V., Garc\u00eda-Cozar, F.J., Ramos-Rodr\u00edguez, J.J., and Melguizo-Rodr\u00edguez, L. (2022). Therapeutic Approach to Alzheimer\u2019s Disease: Current Treatments and New Perspectives. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14061117"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41582-018-0116-6","article-title":"A critical appraisal of amyloid-\u03b2-targeting therapies for Alzheimer disease","volume":"15","author":"Panza","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_4","first-page":"a006189","article-title":"Neuropathological alterations in Alzheimer disease","volume":"1","author":"Frosch","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_5","unstructured":"Marques, B.L., Maciel, G.F., J\u00fanior, M.R.B., Dias, L.D., Scalzo, S., Santos, A.K., Kihara, A.H., da Costa Santiago, H., Parreira, R.C., and Birbrair, A. (2022). Seminars in Cell & Developmental Biology, Elsevier."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101636","DOI":"10.1016\/j.arr.2022.101636","article-title":"Neurogenesis in aging and age-related neurodegenerative diseases","volume":"78","author":"Culig","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1038\/s41591-019-0375-9","article-title":"Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer\u2019s disease","volume":"25","author":"Cafini","year":"2019","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"102280","DOI":"10.1016\/j.pneurobio.2022.102280","article-title":"MST1 mediates neuronal loss and cognitive deficits: A novel therapeutic target for Alzheimer\u2019s disease","volume":"214","author":"Wang","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41420-022-01020-6","article-title":"Hippo signaling pathway and respiratory diseases","volume":"8","author":"Tang","year":"2022","journal-title":"Cell Death Discov."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sileo, P., Simonin, C., Melnyk, P., Chartier-Harlin, M.-C., and Cotelle, P. (2022). Crosstalk between the Hippo Pathway and the Wnt Pathway in Huntington\u2019s Disease and Other Neurodegenerative Disorders. Cells, 11.","DOI":"10.3390\/cells11223631"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13287-021-02686-y","article-title":"Context-dependent transcriptional regulations of YAP\/TAZ in stem cell and differentiation","volume":"13","author":"Luo","year":"2022","journal-title":"Stem. Cell Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.tibs.2020.08.008","article-title":"Hippo signaling in embryogenesis and development","volume":"46","author":"Wu","year":"2021","journal-title":"Trends Biochem. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1101\/gad.1843810","article-title":"A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP)","volume":"24","author":"Zhao","year":"2010","journal-title":"Genes Dev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1002\/dneu.22796","article-title":"Neuronal Hippo signaling: From development to diseases","volume":"81","author":"Sahu","year":"2021","journal-title":"Dev. Neurobiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"281","DOI":"10.3389\/fimmu.2020.00281","article-title":"The role and regulatory mechanism of hippo signaling components in the neuronal system","volume":"11","author":"Cheng","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.pharmthera.2013.12.001","article-title":"Artemisinins: Pharmacological actions beyond anti-malarial","volume":"142","author":"Ho","year":"2014","journal-title":"Pharmacol. Ther."},{"key":"ref_17","first-page":"152962","article-title":"Antitumor activity of an Artemisia annua herbal preparation and identification of active ingredients","volume":"62","author":"Lang","year":"2019","journal-title":"Phytomed. Int. J. Phytother. Phytopharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.19082\/3150","article-title":"A Systematic Review of Anti-malarial Properties, Immunosuppressive Properties, Anti-inflammatory Properties, and Anti-cancer Properties of Artemisia annua","volume":"8","author":"Alesaeidi","year":"2016","journal-title":"Electron. Physician"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.intimp.2019.02.056","article-title":"Immunosuppressive effect of artemisinin and hydroxychloroquine combination therapy on IgA nephropathy via regulating the differentiation of CD4+ T cell subsets in rats","volume":"70","author":"Bai","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"104221","DOI":"10.1016\/j.bioorg.2020.104221","article-title":"Structurally diverse sesquiterpenoids from the aerial parts of Artemisia annua (Qinghao) and their striking systemically anti-inflammatory activities","volume":"103","author":"Qin","year":"2020","journal-title":"Bioorganic Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.vetpar.2018.03.017","article-title":"Artemisinin and Artemisia annua leaves alleviate Eimeria tenella infection by facilitating apoptosis of host cells and suppressing inflammatory response","volume":"254","author":"Jiao","year":"2018","journal-title":"Vet. Parasitol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2018.10.041","article-title":"Artemisinin B Improves Learning and Memory Impairment in AD Dementia Mice by Suppressing Neuroinflammation","volume":"395","author":"Qiang","year":"2018","journal-title":"Neuroscience"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.4196\/kjpp.2015.19.1.21","article-title":"Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L.","volume":"19","author":"Kim","year":"2015","journal-title":"Korean J. Physiol. Pharmacol. Off. J. Korean Physiol. Soc. Korean Soc. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhao, X., Fang, J., Li, S., Gaur, U., Xing, X., Wang, H., and Zheng, W. (2019). Artemisinin Attenuated Hydrogen Peroxide (H2O2)-Induced Oxidative Injury in SH-SY5Y and Hippocampal Neurons via the Activation of AMPK Pathway. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112680"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3390\/antiox3010116","article-title":"Antioxidant Properties of Artemisia annua Extracts in Model Food Emulsions","volume":"3","author":"Skowyra","year":"2014","journal-title":"Antioxidants"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.7150\/ijbs.30536","article-title":"Artemisinin Protects Human Retinal Pigmented Epithelial Cells Against Hydrogen Peroxide-induced Oxidative Damage by Enhancing the Activation of AMP-active Protein Kinase","volume":"15","author":"Li","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1002\/ptr.4758","article-title":"Biochemical and haematological evaluation of repeated dose exposure of male Wistar rats to an ethanolic extract of Artemisia annua","volume":"27","author":"Eteng","year":"2013","journal-title":"Phytother. Res. PTR"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3715","DOI":"10.1002\/jsfa.8879","article-title":"Dietary enzymatically treated Artemisia annua L. improves meat quality, antioxidant capacity and energy status of breast muscle in heat-stressed broilers","volume":"98","author":"Wan","year":"2018","journal-title":"J. Sci. Food Agric."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"430","DOI":"10.3382\/ps\/pex312","article-title":"Effects of dietary supplementation with enzymatically treated Artemisia annua on growth performance, intestinal morphology, digestive enzyme activities, immunity, and antioxidant capacity of heat-stressed broilers","volume":"97","author":"Song","year":"2018","journal-title":"Poult. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Septembre-Malaterre, A., Lalarizo Rakoto, M., Marodon, C., Bedoui, Y., Nakab, J., Simon, E., Hoarau, L., Savriama, S., Strasberg, D., and Guiraud, P. (2020). Artemisia annua, a Traditional Plant Brought to Light. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21144986"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"801","DOI":"10.14336\/AD.2019.0813","article-title":"Artemisinin Improved Neuronal Functions in Alzheimer\u2019s Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK\/CREB Signaling Pathway","volume":"11","author":"Zhao","year":"2020","journal-title":"Aging Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3389\/fnagi.2020.00047","article-title":"Dihydroartemisinin Ameliorates Learning and Memory in Alzheimer\u2019s Disease Through Promoting Autophagosome-Lysosome Fusion and Autolysosomal Degradation for A\u03b2 Clearance","volume":"12","author":"Zhao","year":"2020","journal-title":"Front. Aging Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/acsomega.0c05465","article-title":"Oral Bioavailability Comparison of Artemisinin, Deoxyartemisinin, and 10-Deoxoartemisinin Based on Computer Simulations and Pharmacokinetics in Rats","volume":"6","author":"Fu","year":"2021","journal-title":"ACS Omega"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Thakur, S., Dhapola, R., Sarma, P., Medhi, B., and Reddy, D.H. (2022). Neuroinflammation in Alzheimer\u2019s disease: Current progress in molecular signaling and therapeutics. Inflammation, 1\u201317.","DOI":"10.1007\/s10753-022-01721-1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"ref_36","first-page":"4280","article-title":"Decrease in Adult Neurogenesis and Neuroinflammation Are Involved in Spatial Memory Impairment in the Streptozotocin-Induced Model of Sporadic Alzheimer\u2019s Disease in Rats","volume":"55","author":"Bassani","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/jnr.24551","article-title":"The emerging role of Hippo signaling in neurodegeneration","volume":"98","author":"Sahu","year":"2020","journal-title":"J. Neurosci. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jalz.2017.08.012","article-title":"A systematic integrated analysis of brain expression profiles reveals YAP1 and other prioritized hub genes as important upstream regulators in Alzheimer\u2019s disease","volume":"14","author":"Xu","year":"2018","journal-title":"Alzheimers Dement"},{"key":"ref_39","first-page":"75","article-title":"Hippo\/YAP pathway for targeted therapy","volume":"3","author":"Stahel","year":"2014","journal-title":"Transl. Lung Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.cell.2007.07.019","article-title":"Elucidation of a universal size-control mechanism in Drosophila and mammals","volume":"130","author":"Dong","year":"2007","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1158\/0008-5472.CAN-14-3396","article-title":"YAP promotes malignant progression of Lkb1-deficient lung adenocarcinoma through downstream regulation of survivin","volume":"75","author":"Zhang","year":"2015","journal-title":"Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1038\/s41401-021-00826-x","article-title":"Silibinin relieves UVB-induced apoptosis of human skin cells by inhibiting the YAP-p73 pathway","volume":"43","author":"Liu","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.phrs.2019.03.018","article-title":"Dysregulation of the Hippo pathway signaling in aging and cancer","volume":"143","author":"Yeung","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s11011-019-00516-y","article-title":"Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death","volume":"35","author":"Leong","year":"2020","journal-title":"Metab. Brain Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rajesh, Y., and Kanneganti, T.-D. (2022). Innate immune cell death in neuroinflammation and Alzheimer\u2019s disease. Cells, 11.","DOI":"10.3390\/cells11121885"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0006-8993(97)01202-X","article-title":"Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer\u2019s disease","volume":"780","author":"Kitamura","year":"1998","journal-title":"Brain Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3276","DOI":"10.1111\/febs.14970","article-title":"Apoptotic cell death regulation in neurons","volume":"286","author":"Hollville","year":"2019","journal-title":"FEBS J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"839","DOI":"10.2147\/JAA.S315707","article-title":"YAP promotes cell proliferation and epithelium-derived cytokine expression via NF-\u03baB pathway in nasal polyps","volume":"14","author":"Deng","year":"2021","journal-title":"J. Asthma Allergy"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bhandari, R., Paliwal, J.K., and Kuhad, A. (2020). Neuropsychopathology of autism spectrum disorder: Complex interplay of genetic, epigenetic, and environmental factors. Pers. Food Interv. Ther. Autism Spectr. Disord. Manag., 97\u2013141.","DOI":"10.1007\/978-3-030-30402-7_4"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1862437","DOI":"10.1155\/2019\/1862437","article-title":"Artemether Activation of AMPK\/GSK3\u03b2(ser9)\/Nrf2 Signaling Confers Neuroprotection towards \u03b2-Amyloid-Induced Neurotoxicity in 3xTg Alzheimer\u2019s Mouse Model","volume":"2019","author":"Li","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.neurobiolaging.2017.12.013","article-title":"APP\/Go protein G\u03b2\u03b3-complex signaling mediates A\u03b2 degeneration and cognitive impairment in Alzheimer\u2019s disease models","volume":"64","author":"Bignante","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e12873","DOI":"10.1111\/acel.12873","article-title":"Temporal and regional progression of Alzheimer\u2019s disease-like pathology in 3xTg-AD mice","volume":"18","author":"Belfiore","year":"2019","journal-title":"Aging Cell"},{"key":"ref_53","first-page":"136","article-title":"Role of pro-inflammatory cytokines released from microglia in Alzheimer\u2019s disease","volume":"3","author":"Wang","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1007\/s11011-022-00953-2","article-title":"Reactive gliosis in Alzheimer\u2019s disease: A crucial role for cognitive impairment and memory loss","volume":"37","year":"2022","journal-title":"Metab. Brain Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13195-020-00688-1","article-title":"Microglia prevent beta-amyloid plaque formation in the early stage of an Alzheimer\u2019s disease mouse model with suppression of glymphatic clearance","volume":"12","author":"Feng","year":"2020","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"888989","DOI":"10.3389\/fnagi.2022.888989","article-title":"The role of microglia in Alzheimer\u2019s disease from the perspective of immune inflammation and iron metabolism","volume":"14","author":"Long","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"636","DOI":"10.2174\/1567205014666170117103217","article-title":"Cellular Model of Alzheimer\u2019s Disease: A\u03b21-42 Peptide Induces Amyloid Deposition and a Decrease in Topo Isomerase II\u03b2 and Nurr1 Expression","volume":"14","author":"Negis","year":"2017","journal-title":"Curr. Alzheimer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1248\/bpb.b19-00495","article-title":"Neuroprotective effects of limonene (+) against A\u03b242-induced neurotoxicity in a Drosophila model of Alzheimer\u2019s disease","volume":"43","author":"Shin","year":"2020","journal-title":"Biol. Pharm. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Zhang, T., Song, C., Li, H., Zheng, Y., and Zhang, Y. (2022). Different Extracellular \u03b2-Amyloid (1-42) Aggregates Differentially Impair Neural Cell Adhesion and Neurite Outgrowth through Differential Induction of Scaffold Palladin. Biomolecules, 12.","DOI":"10.3390\/biom12121808"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.18632\/aging.204045","article-title":"YAP: A novel target for Alzheimer\u2019s disease","volume":"14","author":"Xu","year":"2022","journal-title":"Aging"},{"key":"ref_62","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."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1101\/gad.1726608","article-title":"YAP regulates neural progenitor cell number via the TEA domain transcription factor","volume":"22","author":"Cao","year":"2008","journal-title":"Genes Dev."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.molmed.2020.03.010","article-title":"Adult hippocampal neurogenesis in major depressive disorder and Alzheimer\u2019s disease","volume":"26","author":"Berger","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"578211","DOI":"10.3389\/fnmol.2020.578211","article-title":"Does impairment of adult neurogenesis contribute to pathophysiology of alzheimer\u2019s disease? A still open question","volume":"13","author":"Piacentini","year":"2021","journal-title":"Front. Mol. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Sung, P.-S., Lin, P.-Y., Liu, C.-H., Su, H.-C., and Tsai, K.-J. (2020). Neuroinflammation and neurogenesis in Alzheimer\u2019s disease and potential therapeutic approaches. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21030701"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1037\/bne0000027","article-title":"Persistent hyperactivity and distinctive strategy features in the Morris water maze in 3xTg-AD mice at advanced stages of disease","volume":"129","year":"2015","journal-title":"Behav. Neurosci."},{"key":"ref_68","first-page":"e60055","article-title":"Analysis of Learning and Memory Ability in an Alzheimer\u2019s Disease Mouse Model using the Morris Water Maze","volume":"152","author":"Tian","year":"2019","journal-title":"J. Vis. Exp. JoVE"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"64","DOI":"10.34172\/jsums.2019.11","article-title":"Induction of neural stem cell proliferation by iron oxide nanoparticles and magnetic field and Ki67 gene expression in rat hippocampus after ischemia\/reperfusion","volume":"21","author":"Hosseini","year":"2019","journal-title":"J. Shahrekord Univ. Med. Sci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-1-61779-170-3_2","article-title":"Primary neurons in culture and neuronal cell lines for in vitro neurotoxicological studies","volume":"758","author":"Giordano","year":"2011","journal-title":"Methods Mol. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"NS20180207","DOI":"10.1042\/NS20180207","article-title":"Culturing primary neurons from rat hippocampus and cortex","volume":"3","author":"Sahu","year":"2019","journal-title":"Neuronal. Signal."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9 system","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Fu, L., Hu, Y., Song, M., Liu, Z., Zhang, W., Yu, F.-X., Wu, J., Wang, S., Izpisua Belmonte, J.C., and Chan, P. (2019). Up-regulation of FOXD1 by YAP alleviates senescence and osteoarthritis. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000201"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.freeradbiomed.2016.05.023","article-title":"Artemisinin conferred ERK mediated neuroprotection to PC12 cells and cortical neurons exposed to sodium nitroprusside-induced oxidative insult","volume":"97","author":"Zheng","year":"2016","journal-title":"Free Radic Biol. Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"pdb.prot095505","DOI":"10.1101\/pdb.prot095505","article-title":"Analysis of Cell Viability by the MTT Assay","volume":"2018","author":"Kumar","year":"2018","journal-title":"Cold Spring Harb. Protoc."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5259\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:51:55Z","timestamp":1760122315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5259"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":75,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065259"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065259","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]}}}