{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:50:15Z","timestamp":1792788615780,"version":"4.5.0"},"reference-count":40,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alzprotect","id":[{"id":"https:\/\/ror.org\/05kk7gg34","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Alzprotect","id":[{"id":"https:\/\/ror.org\/05kk7gg34","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Michael J. Fox Foundation","award":["MJFF-021163"],"award-info":[{"award-number":["MJFF-021163"]}],"id":[{"id":"https:\/\/ror.org\/03arq3225","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    The pathohistological hallmarks of Parkinson\u2019s disease are aggregated alpha-synuclein and other aggregation-prone proteins (Lewy bodies). Recent studies show mechanistic as well as genetic connections between lysosomal dysfunction and Parkinson\u2019s disease pathology. A direct link between lysosomal function and Parkinson\u2019s disease might be the degradation of alpha-synuclein within the lysosomal system. Progranulin is necessary for maintaining lysosomal function, facilitating the activity of several lysosomal enzymes. Progranulin\u2019s exit from the endoplasmic reticulum and its lysosomal availability depend on an interaction with Prosaposin. AZP2006 (INN: Ezeprogind) is a small lysosomotropic neuroprotective molecule currently in clinical development in Progressive Supranuclear Palsy patients. Its neuroprotective effects involve the Progranulin\/Prosaposin complex. In this study, we investigated the neuroprotective effects of AZP2006 in several Parkinson\u2019s-like models (\n                    <jats:italic>vitro<\/jats:italic>\n                    and\n                    <jats:italic>vivo<\/jats:italic>\n                    ). We showed that AZP2006 was able to counteract a mitochondrial injury as well as the toxicity of alpha-synuclein preformed fibril spreading. We proved that Progranulin was involved in AZP2006\u2019s neuroprotective action, restoring lysosomal homeostasis and ultimately supporting the health of dopaminergic neurons. In light of this evidence, strategies with the aim of improving Progranulin and Prosaposin levels and activity offer a promising therapeutic approach in the context of proteinopathies such as Parkinson\u2019s disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0359269","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:26:38Z","timestamp":1790789198000},"page":"e0359269","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["AZP2006 in Parkinson\u2019s disease models: A promising new neuroprotective treatment involving lysosomal homeostasis and the Progranulin\/Prosaposin complex"],"prefix":"10.1371","volume":"21","author":[{"given":"Noelle","family":"Callizot","sequence":"first","affiliation":[{"name":"Neuro-Sys, Chemin D\u00e9partemental","place":["Gardanne, 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