{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T04:02:36Z","timestamp":1771905756968,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T00:00:00Z","timestamp":1568678400000},"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":"crossref","award":["81503628, 81573819, 81873350"],"award-info":[{"award-number":["81503628, 81573819, 81873350"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2019.01041","type":"journal-article","created":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T13:27:35Z","timestamp":1568726855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Yizhiqingxin Formula Alleviates Cognitive Deficits and Enhances Autophagy via mTOR Signaling Pathway Modulation in Early Onset Alzheimer\u2019s Disease Mice"],"prefix":"10.3389","volume":"10","author":[{"given":"Yang","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiangang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meixia","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2019,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.jalz.2018.02.001","article-title":"Alzheimer\u2019s Association Report 2018 Alzheimer\u2019s disease facts and figures","volume":"14","year":"2018","journal-title":"Alzheimers Dement."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2467","DOI":"10.1080\/15548627.2016.1239003","article-title":"Autophagy flux in CA1 neurons of Alzheimer hippocampus: increased induction overburdens failing lysosomes to propel neuritic dystrophy","volume":"12","author":"Bordi","year":"2016","journal-title":"Autophagy"},{"key":"B3","doi-asserted-by":"publisher","first-page":"13107","DOI":"10.1074\/jbc.M110.100420","article-title":"Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-\u03b2, and tau effects on cognitive impairments","volume":"285","author":"Caccamo","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B4","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.nbd.2006.08.017","article-title":"Characterization of amyloid deposition in the APPswe\/PS1dE9 mouse model of Alzheimer disease","volume":"24","author":"Garcia-Alloza","year":"2006","journal-title":"Neurobiol Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1478-811X-12-23","article-title":"Signaling pathway cross talk in Alzheimer\u2019s disease","volume":"12","author":"Godoy","year":"2014","journal-title":"Cell Commun. Signal."},{"key":"B6","doi-asserted-by":"publisher","first-page":"332","DOI":"10.3109\/10641963.2014.972560","article-title":"Anti-hypertensive and renoprotective effects of berberine in spontaneously hypertensive rats","volume":"37","author":"Guo","year":"2015","journal-title":"Clin. Exp. Hypertens."},{"key":"B7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/hmg\/ddh019","article-title":"Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase","volume":"13","author":"Jankowsky","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2013.01.012","article-title":"The prevalence of dementia in urban and rural areas of China","volume":"10","author":"Jia","year":"2014","journal-title":"Alzheimers Dement."},{"key":"B9","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.jalz.2017.12.006","article-title":"The cost of Alzheimer\u2019s disease in China and re-estimation of costs worldwide","volume":"14","author":"Jia","year":"2018","journal-title":"Alzheimers Dement."},{"key":"B10","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.phrs.2014.02.008","article-title":"Temsirolimus promotes autophagic clearance of amyloid-\u03b2 and provides protective effects in cellular and animal models of Alzheimer\u2019s disease","volume":"81","author":"Jiang","year":"2014","journal-title":"Pharmacol. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1172\/JCI73939","article-title":"MTOR: a pharmacologic target for autophagy regulation","volume":"125","author":"Kim","year":"2015","journal-title":"J. Clin. Invest."},{"key":"B12","doi-asserted-by":"publisher","first-page":"396","DOI":"10.3390\/cells1030396","article-title":"LC3-associated phagocytosis (LAP): connections with host autophagy","volume":"1","author":"Lai","year":"2012","journal-title":"Cells"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1084\/jem.20132451","article-title":"Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer\u2019s disease","volume":"211","author":"Lee","year":"2014","journal-title":"J. Exp. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1038\/cdd.2010.115","article-title":"Negative regulation of autophagy","volume":"17","author":"Liang","year":"2010","journal-title":"Cell Death Differ."},{"key":"B15","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.bbr.2016.10.031","article-title":"Autophagy-lysosome dysfunction is involved in Abeta deposition in STZ-induced diabetic rats","volume":"320","author":"Ma","year":"2017","journal-title":"Behav. Brain Res."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025416","article-title":"Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits","volume":"6","author":"Majumder","year":"2011","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.celrep.2013.08.042","article-title":"A\u03b2 secretion and plaque formation depend on autophagy","volume":"5","author":"Nilsson","year":"2013","journal-title":"Cell Rep."},{"key":"B18","doi-asserted-by":"publisher","first-page":"941","DOI":"10.2741\/s310","article-title":"The role of mTOR signaling in Alzheimer disease","volume":"4","author":"Oddo","year":"2012","journal-title":"Front. Biosci. (Schol Ed)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.nbd.2015.03.014","article-title":"mTOR signaling in aging and neurodegeneration: at the crossroad between metabolism dysfunction and impairment of autophagy","volume":"84","author":"Perluigi","year":"2015","journal-title":"Neurobiol. Dis."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1172\/JCI33585","article-title":"The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid \u03b2 accumulation in mice","volume":"118","author":"Pickford","year":"2008","journal-title":"J. Clin. Invest."},{"key":"B21","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s10059-013-0140-8","article-title":"Autophagy: a critical regulator of cellular metabolism and homeostasis","volume":"36","author":"Ryter","year":"2013","journal-title":"Mol. Cells"},{"key":"B22","doi-asserted-by":"publisher","first-page":"224","DOI":"10.4103\/1673-5374.226389","article-title":"Is it time to rethink the Alzheimer\u2019s disease drug development strategy by targeting its silent phase","volume":"13","author":"Souchet","year":"2018","journal-title":"Neural Regen Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3233\/JAD-131124","article-title":"Differential activation of mTOR complex 1 signaling in human brain with mild to severe Alzheimer\u2019s disease","volume":"38","author":"Sun","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"15008","DOI":"10.1038\/npjamd.2015.8","article-title":"The mammalian target of rapamycin at the crossroad between cognitive aging and Alzheimer\u2019s disease","volume":"1","author":"Talboom","year":"2015","journal-title":"NPJ Aging Mech. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"84","DOI":"10.4161\/auto.1.2.1697","article-title":"Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy","volume":"1","author":"Tanida","year":"2005","journal-title":"Autophagy"},{"key":"B26","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/jnc.13037","article-title":"Targeting mTOR to reduce Alzheimer-related cognitive decline: from current hits to future therapies","volume":"17","author":"Tramutola","year":"2017","journal-title":"Expert Rev. Neurother."},{"key":"B27","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s00418-008-0406-y","article-title":"Autophagy\u2013physiology and pathophysiology","volume":"129","author":"Uchiyama","year":"2008","journal-title":"Histochem. Cell Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3037","DOI":"10.2147\/NDT","article-title":"The Chinese herbal formula Fuzheng Quxie decoction attenuates cognitive impairment and protects cerebrovascular function in SAMP8 mice","volume":"14","author":"Wang","year":"2018","journal-title":"Neuropsychiatr Dis. Treat."},{"key":"B29","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/1750-1326-5-46","article-title":"Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model","volume":"5","author":"Wang","year":"2010","journal-title":"Mol. Neurodegener."},{"key":"B30","doi-asserted-by":"publisher","first-page":"5934254","DOI":"10.1155\/2017\/5934254","article-title":"Fuzheng Quxie decoction ameliorates learning and memory impairment in SAMP8 mice by decreasing tau hyperphosphorylation","volume":"2017","author":"Yang","year":"2017","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.febslet.2007.11.078","article-title":"Parallel increase in p70 kinase activation and tau phosphorylation (S262) with A\u03b2 overproduction","volume":"582","author":"Zhou","year":"2008","journal-title":"FEBS Lett."},{"key":"B32","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1007\/s12035-013-8457-z","article-title":"Autophagy modulation for Alzheimer\u2019s disease therapy","volume":"48","author":"Zhu","year":"2013","journal-title":"Mol. Neurobiol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01041\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,17]],"date-time":"2019-09-17T13:27:39Z","timestamp":1568726859000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2019.01041\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,17]]},"references-count":32,"alternative-id":["10.3389\/fphar.2019.01041"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2019.01041","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,17]]},"article-number":"1041"}}