{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T05:31:14Z","timestamp":1768714274783,"version":"3.49.0"},"reference-count":86,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"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>Oxidation of the neurotransmitter, dopamine (DA), is a pathological hallmark of Parkinson\u2019s disease (PD). Oxidized DA forms adducts with proteins which can alter their functionality. \u03b1B-crystallin and Hsp27 are intracellular, small heat-shock molecular chaperone proteins (sHsps) which form the first line of defense to prevent protein aggregation under conditions of cellular stress. In vitro, the effects of oxidized DA on the structure and function of \u03b1B-crystallin and Hsp27 were investigated. Oxidized DA promoted the cross-linking of \u03b1B-crystallin and Hsp27 to form well-defined dimer, trimer, tetramer, etc., species, as monitored by SDS-PAGE. Lysine residues were involved in the cross-links. The secondary structure of the sHsps was not altered significantly upon cross-linking with oxidized DA but their oligomeric size was increased. When modified with a molar equivalent of DA, sHsp chaperone functionality was largely retained in preventing both amorphous and amyloid fibrillar aggregation, including fibril formation of mutant (A53T) \u03b1-synuclein, a protein whose aggregation is associated with autosomal PD. In the main, higher levels of sHsp modification with DA led to a reduction in chaperone effectiveness. In vivo, DA is sequestered into acidic vesicles to prevent its oxidation and, intracellularly, oxidation is minimized by mM levels of the antioxidant, glutathione. In vitro, acidic pH and glutathione prevented the formation of oxidized DA-induced cross-linking of the sHsps. Oxidized DA-modified \u03b1B-crystallin and Hsp27 were not cytotoxic. In a cellular context, retention of significant chaperone functionality by mildly oxidized DA-modified sHsps would contribute to proteostasis by preventing protein aggregation (particularly of \u03b1-synuclein) that is associated with PD.<\/jats:p>","DOI":"10.3390\/ijms22073700","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T04:13:51Z","timestamp":1617336831000},"page":"3700","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Effect of Oxidized Dopamine on the Structure and Molecular Chaperone Function of the Small Heat-Shock Proteins, \u03b1B-Crystallin and Hsp27"],"prefix":"10.3390","volume":"22","author":[{"given":"Junna","family":"Hayashi","sequence":"first","affiliation":[{"name":"Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Ton","sequence":"additional","affiliation":[{"name":"Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sparsh","family":"Negi","sequence":"additional","affiliation":[{"name":"Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia"},{"name":"Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel E. K. M.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean L.","family":"Pountney","sequence":"additional","affiliation":[{"name":"School of Medical Science, Griffith University, Gold Coast, QLD 4215, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6273-784X","authenticated-orcid":false,"given":"Thomas","family":"Preiss","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, John Curtin School of Medical Research, The Australian National University, Acton, ACT 2601, Australia"},{"name":"Victor Chang Cardiac Research Institute, Sydney, NSW 2010, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2441-8108","authenticated-orcid":false,"given":"John A.","family":"Carver","sequence":"additional","affiliation":[{"name":"Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"aac4354","DOI":"10.1126\/science.aac4354","article-title":"In vivo aspects of protein folding and quality control","volume":"353","author":"Balchin","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a004440","DOI":"10.1101\/cshperspect.a004440","article-title":"Aging as an event of proteostasis collapse","volume":"3","author":"Taylor","year":"2011","journal-title":"Cold Spring Harb. 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