{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:35:07Z","timestamp":1780504507759,"version":"3.54.1"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,10,3]],"date-time":"2016-10-03T00:00:00Z","timestamp":1475452800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24406004"],"award-info":[{"award-number":["24406004"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24651061"],"award-info":[{"award-number":["24651061"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["14J06235"],"award-info":[{"award-number":["14J06235"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Abstract<\/jats:title>Parkinson's disease (PD<\/jats:styled-content>) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD<\/jats:styled-content>\u2010related neurotoxin MPP<\/jats:styled-content>+<\/jats:sup> suggest autophagy involvement in the pathogenesis of PD<\/jats:styled-content>, the effect of MPP<\/jats:styled-content>+<\/jats:sup> on autophagic processes under mild exposure, which mimics the slow progressive nature of PD<\/jats:styled-content>, remains largely unclear. We examined the effect of mild MPP<\/jats:styled-content>+<\/jats:sup> exposure (10 and 200\u00a0\u03bcM for 48\u00a0h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP<\/jats:styled-content>+<\/jats:sup> toxicity (2.5 and 5\u00a0mM<\/jats:styled-content> for 24 h). In SH<\/jats:styled-content>\u2010SY<\/jats:styled-content>5Y cells, mild MPP<\/jats:styled-content>+<\/jats:sup> exposure predominantly inhibited autophagosome degradation, whereas acute MPP<\/jats:styled-content>+<\/jats:sup> exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP<\/jats:styled-content>+<\/jats:sup> exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP<\/jats:styled-content>+<\/jats:sup> exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP<\/jats:styled-content>+<\/jats:sup> exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP<\/jats:styled-content>+<\/jats:sup> exposure and mechanistic differences between mild and acute MPP<\/jats:styled-content>+<\/jats:sup> toxicities. Mild MPP<\/jats:styled-content>+<\/jats:sup> toxicity impaired autophagosome degradation through novel lysosomal acidity\u2010independent mechanisms. Sustained mild lysosomal damage may contribute to PD<\/jats:styled-content>.<\/jats:p><\/jats:sec>\nimage<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nWe examined the effects of MPP+<\/jats:sup> on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH\u2010SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP+<\/jats:sup> exposure. Mechanistic differences between acute and mild MPP+<\/jats:sup> toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause of Parkinson's disease.<\/jats:p>Cover Image<\/jats:bold> for this issue: doi: 10.1111\/jnc.13338<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13700","type":"journal-article","created":{"date-parts":[[2016,6,16]],"date-time":"2016-06-16T15:46:51Z","timestamp":1466092011000},"page":"294-308","source":"Crossref","is-referenced-by-count":34,"title":["Mild MPP<\/scp>+<\/sup> exposure impairs autophagic degradation through a novel lysosomal acidity\u2010independent mechanism"],"prefix":"10.1111","volume":"139","author":[{"given":"Masatsugu","family":"Miyara","sequence":"first","affiliation":[{"name":"Graduate School of Biomedical and Health Sciences Hiroshima University Hiroshima Japan"},{"name":"Global Career Design Center Hiroshima University Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaichiro","family":"Kotake","sequence":"additional","affiliation":[{"name":"Graduate School 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