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SiNPs may cause adverse effects in the brain including neurotoxicity, neuroinflammation, neurodegeneration, and enhancing levels of amyloid beta (A\u03b2) protein\u2014all pathological hallmarks of Alzheimer\u2019s disease. Therefore, the extent to which SiNPs influence A\u03b2 generation and the underlying mechanisms by which this occurs deserve investigation. Our studies were focused on the effects of SiNPs on endolysosomes which uptake, traffic, and mediate the actions of SiNPs. These organelles are also where amyloidogenesis largely originates. We found that SiNPs, in primary cultured hippocampal neurons, accumulated in endolysosomes and caused a rapid and persistent deacidification of endolysosomes. SiNPs significantly reduced endolysosome calcium stores as indicated by a significant reduction in the ability of the lysosomotropic agent glycyl-l-phenylalanine 2-naphthylamide (GPN) to release calcium from endolysosomes. SiNPs increased A\u03b2<jats:sub>1\u201340<\/jats:sub> secretion, whereas 2 agents that acidified endolysosomes, ML-SA1 and CGS21680, blocked SiNP-induced deacidification and increased generation of A\u03b2<jats:sub>1\u201340<\/jats:sub>. Our findings suggest that SiNP-induced deacidification of and calcium release from endolysosomes might be mechanistically linked to increased amyloidogenesis. The use of SiNPs might not be the best nanomaterial for therapeutic strategies against Alzheimer\u2019s disease and other neurological disorders linked to endolysosome dysfunction. <\/jats:p>","DOI":"10.1139\/cjpp-2018-0401","type":"journal-article","created":{"date-parts":[[2018,10,12]],"date-time":"2018-10-12T21:34:34Z","timestamp":1539380074000},"page":"297-305","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Effects of silica nanoparticles on endolysosome function in primary cultured neurons"],"prefix":"10.1139","volume":"97","author":[{"given":"Yan","family":"Ye","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koffi L.","family":"Lakpa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Dakota, Grand Forks, ND 58202, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Wollenzien","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia Xiaojun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of North Dakota, Grand Forks, ND 58202, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Geiger","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58203, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjt022"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0210-14.2014"},{"key":"refg3\/ref3","doi-asserted-by":"publisher","DOI":"10.1039\/c2cc16306c"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1021\/la049137j"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.1039\/C3CS60273G"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2012.06.014"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0800-08.2008"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408746200"},{"key":"refg9\/ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.03.004"},{"key":"refg10\/ref10","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.3233\/JAD-2010-101323","volume":"22","author":"Chen X.","year":"2010","journal-title":"J. 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