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Project","award":["2023JCYJ072"],"award-info":[{"award-number":["2023JCYJ072"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Dysfunction of the lysosome and autophagy\u2013lysosome pathway is closely associated with various diseases, such as neurodegenerative diseases, non-alcoholic fatty liver disease (NAFLD), etc. Additionally, chloroquine is a clinically widely used drug for treating malaria and autoimmune diseases, but long-term or high-dose administration may lead to significant toxic side effects. Attapulgite (ATT), a natural nanomaterial with excellent adsorption capacity and biocompatibility, herein demonstrated a novel biological function in regulating the lysosomal and autophagy\u2013lysosome pathway. ATT could be effectively internalized into lysosome-related acidic compartments. Further study revealed that ATT could restore lysosomal pH, activate cathepsin D, alleviate autophagy blockage in chloroquine-treated cells, and reduce chloroquine-elicited cell death. In a cell model related to Huntington\u2019s disease, treatment with ATT reinforced the degradation of the mutant huntingtin proteins by increasing cathepsin D maturation and autophagy flux. ATT could also promote lipid droplet clearance in hepatocytes with palmitic acid-induced steatosis, reduce hepatic lipid accumulation, and improve fasting blood glucose in high-fat-diet-induced NAFLD mice. These findings establish ATT as a lysosomal modulator, providing a foundation for its therapeutic potential in mitigating the adverse effects associated with long-term chloroquine use, especially improving neurodegenerative and metabolic disorders.<\/jats:p>","DOI":"10.3390\/biom15050728","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Recovery of Lysosomal Acidification and Autophagy Flux by Attapulgite Nanorods: Therapeutic Potential for Lysosomal Disorders"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8840-7131","authenticated-orcid":false,"given":"Yuanjing","family":"Hao","sequence":"first","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3252-2716","authenticated-orcid":false,"given":"Xinru","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7783-243X","authenticated-orcid":false,"given":"Xiaodan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2341-9824","authenticated-orcid":false,"given":"Zhaoying","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4084-5329","authenticated-orcid":false,"given":"Zhiyuan","family":"Jing","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9705-6646","authenticated-orcid":false,"given":"Guilong","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3926-499X","authenticated-orcid":false,"given":"Yuxue","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8121-2633","authenticated-orcid":false,"given":"Na","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5786-6580","authenticated-orcid":false,"given":"Pengfei","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, Yantai 264003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41580-019-0185-4","article-title":"Lysosomes as dynamic regulators of cell and organismal homeostasis","volume":"21","author":"Ballabio","year":"2019","journal-title":"Nat. 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