{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:58:50Z","timestamp":1793066330449,"version":"4.5.0"},"reference-count":246,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T00:00:00Z","timestamp":1645401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A major hallmark of Parkinson\u2019s disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of \u03b1-synuclein protein aggregates. A triad contribution of \u03b1-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated \u03b1-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and \u03b1-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.<\/jats:p>","DOI":"10.3390\/ijms23042378","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:47:45Z","timestamp":1645476465000},"page":"2378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Ferritinophagy and \u03b1-Synuclein: Pharmacological Targeting of Autophagy to Restore Iron Regulation in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Matthew K.","family":"Boag","sequence":"first","affiliation":[{"name":"School of Pharmacy and Medical Science, Griffith University, Gold Coast 4222, Australia"},{"name":"Griffith Institute of Drug Discovery, Griffith University, Nathan 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angus","family":"Roberts","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Science, Griffith University, Gold Coast 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-5857","authenticated-orcid":false,"given":"Vladimir N.","family":"Uversky","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linlin","family":"Ma","sequence":"additional","affiliation":[{"name":"Griffith Institute of Drug Discovery, Griffith University, Nathan 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Des R.","family":"Richardson","sequence":"additional","affiliation":[{"name":"Griffith Institute of Drug Discovery, Griffith University, Nathan 4111, Australia"},{"name":"Centre for Cancer Cell Biology and Drug Discovery, School of Environment and Sciences, Griffith University, Nathan 4111, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean L.","family":"Pountney","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Science, Griffith University, Gold Coast 4222, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1176\/jnp.14.2.223","article-title":"An essay on the shaking palsy","volume":"14","author":"Parkinson","year":"2002","journal-title":"J. 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