{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:00:55Z","timestamp":1790265655711,"version":"4.1.0"},"reference-count":146,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Protein misfolding neurodegenerative diseases are invariably fatal conditions with a paucity of available and universally embraced disease modifying therapies. It is crucial, therefore, to identify additional potential candidate molecules and\/or targets with which to work toward human trials. In this mini-review, I will highlight the recent discoveries of compounds that physically associate with the lysosome to enhance or restore its activity. One potential target for the development of additional therapeutics that emerges from the consideration of these molecules is the proton pump responsible for acidification of the lysosomal lumen, the vacuolar H\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase. While the approach of directly targeting lysosomal activity remains experimental at present, the wealth of evidence pointing to the involvement of the endolysosomal-autophagic system across protein misfolding neurodegenerative diseases raises the tantalizing possibility that this therapeutic modality could have broad applicability.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2026.1941231","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:40:27Z","timestamp":1790163627000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["One organelle to rule them all: enhancement of lysosomal activity as a therapeutic modality for protein misfolding neurodegenerative diseases"],"prefix":"10.3389","volume":"20","author":[{"given":"Robert C. C.","family":"Mercer","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, College of Graduate Studies, Midwestern University","place":["Glendale, AZ, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1126\/science.aaz2924","article-title":"Structure of V-ATPase from the mammalian brain","volume":"367","author":"Abbas","year":"2020","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.coph.2019.04.013","article-title":"Autophagy pathways in the treatment of prion diseases","volume":"44","author":"Abdelaziz","year":"2019","journal-title":"Curr. Opin. 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