{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:55:04Z","timestamp":1790506504452,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,3,2]],"date-time":"2011-03-02T00:00:00Z","timestamp":1299024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AG\u201009464"],"award-info":[{"award-number":["AG\u201009464"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:p>\n                    The hallmarks of Alzheimer's disease are the aggregates of amyloid\u2010\u03b2 (A\u03b2) peptide and tau protein. Autophagy is one major cellular pathway leading to the removal of aggregated proteins. We examined the possibility of inducing autophagy to reduce A\u03b2 peptide and the amyloid precursor protein (APP)\u2010derived fragment APP\u2010CTF levels in cell lines and primary neuronal cultures. We found that induction of autophagy either by small\u2010molecule enhancers of rapa\u2010mycin (SMER)28, a small\u2010molecule enhancer of autophagy, or following starvation greatly decreased the levels of A\u03b2 peptide (apparent EC\n                    <jats:sub>50<\/jats:sub>\n                    of ~10 \u00b5M) and APP\u2010CTF (apparent EC\n                    <jats:sub>50<\/jats:sub>\n                    of ~20 \u00b5M) in a \u03b3\u2010secretase\u2010independent manner. Pharmacological inhibition of autophagy led to a significant accumulation of A\u03b2 peptide and APP\u2010CTF and diminished the effect of SMER28. Three essential components of the autophagic pathway, autophagy\u2010related protein (Atg)5, Beclin1, and Ulk1, were shown to be involved in the degradation of A\u03b2 and APP\u2010CTF, and Atg5 was necessary for the effect of SMER28. In addition, the autophagic marker light chain 3\u2010II cocompartmentalized with APP\u2010CTF. These results support the involvement of autophagy in the clearance of A\u03b2 and APP\u2010CTF. We therefore propose that small molecule enhancers of autophagy, such as SMER28, may have therapeutic potential for the treatment of Alzheimer's disease and other proteinopathies.\u2014Tian, Y., Bustos, V., Flajolet, M., Greengard, P. A small\u2010molecule enhancer of autophagy decreases levels of A\u03b2 and APP\u2010CTF\n                    <jats:italic>via<\/jats:italic>\n                    Atg5\u2010dependent autophagy pathway.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 1934\u20101942 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-175158","type":"journal-article","created":{"date-parts":[[2011,3,2]],"date-time":"2011-03-02T23:07:03Z","timestamp":1299107223000},"page":"1934-1942","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":200,"title":["A small\u2010molecule enhancer of autophagy decreases levels of A\u03b2 and APP\u2010CTF\n                    <b>\n                      <i>via<\/i>\n                      Atg5\u2010dependent autophagy pathway\n                    <\/b>"],"prefix":"10.1096","volume":"25","author":[{"given":"Yuan","family":"Tian","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience Rockefeller University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Bustos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience Rockefeller University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Flajolet","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience Rockefeller University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Greengard","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Neuroscience Rockefeller University New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,3,2]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/331528a0"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.9.5.7896005"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05554.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/64.2.113"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03029"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1717"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2010.02.008"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1247\/csf.27.421"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03402040"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e03-09-0704"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2008.00701.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ceb.2009.12.004","article-title":"The role of the Atg1\/ULK1 complex in autophagy regulation","volume":"22","author":"Mizushima N.","journal-title":"Curr Opin Cell Biol."},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08-01-0080"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.tcb.2010.03.002","article-title":"The Beclin 1\u2010VPS34 complex\u2013at the crossroads of autophagy and beyond","volume":"20","author":"Funderburk S. 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