{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:12:12Z","timestamp":1787814732150,"version":"build-2784847793"},"reference-count":197,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T00:00:00Z","timestamp":1536796800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 2018"],"award-info":[{"award-number":["Ricerca Corrente 2018"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autophagy primarily works to counteract nutrient deprivation that is strongly engaged during starvation and hypoxia, which happens in hypoperfusion. Nonetheless, autophagy is slightly active even in baseline conditions, when it is useful to remove aged proteins and organelles. This is critical when the mitochondria and\/or proteins are damaged by toxic stimuli. In the present review, we discuss to that extent the recruitment of autophagy is beneficial in counteracting brain hypoperfusion or, vice-versa, its overactivity may per se be detrimental for cell survival. While analyzing these opposite effects, it turns out that the autophagy activity is likely not to be simply good or bad for cell survival, but its role varies depending on the timing and amount of autophagy activation. This calls for the need for an appropriate autophagy tuning to guarantee a beneficial effect on cell survival. Therefore, the present article draws a theoretical pattern of autophagy activation, which is hypothesized to define the appropriate timing and intensity, which should mirrors the duration and severity of brain hypoperfusion. The need for a fine tuning of the autophagy activation may explain why confounding outcomes occur when autophagy is studied using a rather simplistic approach.<\/jats:p>","DOI":"10.3390\/ijms19092756","type":"journal-article","created":{"date-parts":[[2018,9,13]],"date-time":"2018-09-13T11:46:04Z","timestamp":1536839164000},"page":"2756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Ambiguous Effects of Autophagy Activation Following Hypoperfusion\/Ischemia"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-7160","authenticated-orcid":false,"given":"Michela","family":"Ferrucci","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3566-4889","authenticated-orcid":false,"given":"Francesca","family":"Biagioni","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli (IS), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3150-1863","authenticated-orcid":false,"given":"Larisa","family":"Ryskalin","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0185-2099","authenticated-orcid":false,"given":"Fiona","family":"Limanaqi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gambardella","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli (IS), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Frati","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli (IS), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3883-5084","authenticated-orcid":false,"given":"Francesco","family":"Fornai","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Via Roma 55, 56126 Pisa, Italy"},{"name":"IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli (IS), Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1038\/nature05291","article-title":"The roles of intracellular protein-degradation pathways in neurodegeneration","volume":"443","author":"Rubinsztein","year":"2006","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1126\/science.1141448","article-title":"Adapting proteostasis for disease intervention","volume":"319","author":"Balch","year":"2008","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1083\/jcb.201005144","article-title":"Protein homeostasis and aging in neurodegeneration","volume":"190","author":"Douglas","year":"2010","journal-title":"J. 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