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In\n                    <jats:italic>SorL1<\/jats:italic>\n                    \u2010null rats, a disorder of the global endosome\u2010lysosome network (ELN) is found in hippocampal neurons. Deletion of\n                    <jats:italic>amyloid precursor protein<\/jats:italic>\n                    (\n                    <jats:italic>APP<\/jats:italic>\n                    ) in\n                    <jats:italic>SorL1<\/jats:italic>\n                    \u2010null rats could not completely rescue the neuronal abnormalities in the ELN of the hippocampus and the impairment of spatial memory in\n                    <jats:italic>SorL1<\/jats:italic>\n                    \u2010null young rats. These in vivo observations indicated that APP is one of the cargoes of\n                    <jats:italic>SorL1<\/jats:italic>\n                    in the regulation of the ELN, which affects hippocampal\u2010dependent memory. When\n                    <jats:italic>SorL1<\/jats:italic>\n                    is depleted, the endolysosome takes up more of the lysosome flux and damages lysosomal digestion, leading to pathological lysosomal storage and disturbance of cholesterol and iron homeostasis in the hippocampus. These disturbances disrupt the original homeostasis of the material\u2010energy\u2010subcellular structure and reprogram energy metabolism based on fatty acids in the\n                    <jats:italic>SorL1<\/jats:italic>\n                    \u2010null hippocampus, instead of glucose. Although fatty acid oxidation increases ATP supply, it cannot reduce the levels of the harmful byproduct ROS during oxidative phosphorylation, as it does in glucose catabolism. Therefore, the\n                    <jats:italic>SorL1<\/jats:italic>\n                    \u2010null rats exhibit hippocampal degeneration, and their spatial memory is impaired. Our research sheds light on the pathology of\n                    <jats:italic>SorL1<\/jats:italic>\n                    deficiency in AD.\n                  <\/jats:p>","DOI":"10.1002\/advs.202407709","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T09:54:49Z","timestamp":1725357289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Endo\u2010Lysosomal Network Disorder Reprograms Energy Metabolism in\n                    <i>SorL1<\/i>\n                    \u2010Null Rat Hippocampus"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9745-3844","authenticated-orcid":false,"given":"Yajie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Disease Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University  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