{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:23:56Z","timestamp":1793316236910,"version":"4.5.0"},"reference-count":82,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T00:00:00Z","timestamp":1777075200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting over 10 million people worldwide. It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra and the accumulation of misfolded \u03b1\u2010synuclein (\u03b1Syn) in intracellular inclusions known as Lewy bodies. Emerging evidence links \u03b1Syn accumulation to impaired lysosomal acidification and defective autophagy\u2010lysosomal degradation, which are central to disease progression. To address this lysosomal dysfunction, we engineered a novel type of lysosome\u2010targeted acidic nanoparticles (AcNPs) based on a biodegradable copolymer, poly(ethylene tetrafluorosuccinate\u2010co\u2010succinate) (PEFSU). These nanomaterials were developed to locally acidify impaired lysosomes and restore their degradative capacity. We evaluated their therapeutic potential in two familial PD models: SH\u2010SY5Y neuroblastoma cells overexpressing A30P \u03b1Syn and A30P \u03b1Syn transgenic\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    . In vitro, AcNPs effectively restored lysosomal pH, enhanced autophagic clearance of \u03b1Syn, improved mitochondrial function, and rescued A30P \u03b1Syn\u2010induced cytotoxicity. In vivo, AcNPs treatment reduced \u03b1Syn burden, preserved dopaminergic neurons, and improved motor function in flies. This study demonstrates the first application of lysosome\u2010acidifying polymeric nanoparticles in familial PD models and highlights the promise of rationally engineered pH\u2010modulating nanomaterials as therapeutic agents for PD and other neurodegenerative diseases driven by lysosomal dysfunction and protein aggregation.\n                  <\/jats:p>","DOI":"10.1002\/adhm.202502906","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T11:15:42Z","timestamp":1777115742000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lysosome\u2010Acidifying Nanoparticles Rescue A30P \u03b1\u2010Synuclein Induced Neuronal Death in Cellular and\n                    <i>Drosophila<\/i>\n                    Models of Parkinson's Disease"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2717-4484","authenticated-orcid":false,"given":"Chih 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