{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:33:30Z","timestamp":1789731210473,"version":"4.0.1"},"reference-count":17,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T00:00:00Z","timestamp":1656374400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["R21AI142649"],"award-info":[{"award-number":["R21AI142649"]}]},{"name":"National Institutes of Health (NIH)","award":["R03AG059554"],"award-info":[{"award-number":["R03AG059554"]}]},{"name":"National Institutes of Health (NIH)","award":["R03AA026516"],"award-info":[{"award-number":["R03AA026516"]}]},{"name":"National Institutes of Health (NIH)","award":["R21AG073919"],"award-info":[{"award-number":["R21AG073919"]}]},{"name":"National Institutes of Health (NIH)","award":["R03AG071596"],"award-info":[{"award-number":["R03AG071596"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>The current belief is that amino acid sequences in protein structures are defined by DNA sequences. I challenge this concept by hypothesizing that an arginine (Arg) residue in the protein structure can post-translationally be converted to a proline (Pro) residue through a redox mechanism. Reactive oxygen species promote the formation of protein carbonylation, particularly on Arg and Pro residues, which both produce glutamyl semialdehyde. Our previous studies suggested that the Pro-to-glutamyl semialdehyde reaction could be reversible in the biological system, thereby opening up a pathway for the conversion of Arg to glutamyl semialdehyde by oxidation, and subsequently, to Pro by reduction in the protein structure. Our mass spectrometry and immunoblotting experiments provided evidence of the occurrence of the Arg-to-Pro conversion at position 108 (R108P) of the peroxiredoxin 6 (Prx6) protein in biological tissues and cells. In the human brain, Prx6 (R108P) occurs, and some Alzheimer\u2019s brains exhibit increased Prx6 (R108P) levels, while others show decreased levels, indicating the complexity of redox processes in the disease state. I propose that Prx6 (R108P), as well as other post-translationally regulated protein Arg-to-Pro conversions, occur in the human body and play physiological and pathological roles.<\/jats:p>","DOI":"10.3390\/life12070967","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T01:48:38Z","timestamp":1656467318000},"page":"967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Post-Translationally Regulated Protein Arginine-to-Proline Conversion in Alzheimer\u2019s Brains"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6689-0497","authenticated-orcid":false,"given":"Yuichiro Justin","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20007, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/227561a0","article-title":"Central dogma of molecular biology","volume":"227","author":"Crick","year":"1970","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1056\/NEJM199407073310109","article-title":"DNA and the genetic code","volume":"331","author":"Rosenthal","year":"1994","journal-title":"N. 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Sci., 22.","DOI":"10.3390\/ijms22041687"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1089\/ars.2010.3412","article-title":"Peroxiredoxin 6: A bifunctional enzyme with glutathione peroxidase and phospholipase A2 activities","volume":"15","author":"Fisher","year":"2011","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.abb.2016.12.003","article-title":"Peroxiredoxin 6 in the repair of peroxidized cell membranes and cell signaling","volume":"617","author":"Fisher","year":"2017","journal-title":"Arch. Biochem. 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