{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T14:07:56Z","timestamp":1747058876737},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The abnormal activity of PP2A, a dominant member of type 2A serine\/threonine protein phosphatase, has been implicated in the development of Alzheimer\u2019s disease (AD) and dementia with Lewy bodies (DLB). PP2A is a holoenzyme, and protein methylation of the catalytic subunit, PP2Ac, alters the complex composition. A decrease in PP2Ac methylation levels has been reported in AD and DLB. Aging is the most common risk factor for AD and DLB, but the relationship between aging and PP2A has not been studied in detail. Cynomolgus monkey show increased phosphorylation levels of tau and \u03b1-synuclein with aging. In this study, we investigated the alterations in the PP2A activity regulation with aging in monkey brains from 2 to 43\u00a0years of age using fractionated proteins. We found that type 2A protein phosphatase activity decreased with aging in cytoplasmic and nuclear-soluble fractions. PP2Ac methylation level was decreased in cytoplasmic and sarkosyl-insoluble fractions. A principal component analysis using PP2Ac, demethylated PP2Ac and PP2A methylesterase PME-1 levels in cytoplasmic and nuclear-soluble fractions as attributes showed that aged monkeys were in the same cluster. Our results show that brain aging in cynomolgus monkeys is closely related to changes in PP2A methylation.<\/jats:p>","DOI":"10.1093\/jb\/mvad006","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T02:23:11Z","timestamp":1674786191000},"page":"435-445","source":"Crossref","is-referenced-by-count":5,"title":["Age-related alterations in protein phosphatase 2A methylation levels in brains of cynomolgus monkeys: a pilot study"],"prefix":"10.1093","volume":"173","author":[{"given":"Sana","family":"Ando","sequence":"first","affiliation":[{"name":"Yamaguchi University Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, , 1677-1 Yoshida, Yamaguchi 753-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Yamaguchi University Laboratory of Veterinary Pathology, Joint Faculty of Veterinary Medicine, , 1677-1 Yoshida, Yamaguchi 753-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shusaku","family":"Shibutani","sequence":"additional","affiliation":[{"name":"Yamaguchi University Laboratory of Veterinary Hygiene, Joint Faculty of Veterinary Medicine, , 1677-1 Yoshida, Yamaguchi 753-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"Health and Nutrition Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, , 1-1 Hachimandai, Tsukuba, Ibaraki, 305-0843, Japan"},{"name":"Okayama University of Science, 1-3 Ikoinooka, Imabari, Ehime, 794-8555, Japan Laboratory of Laboratory Animal, Department of Veterinary Associated Science, Faculty of Veterinary Medicine,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhiro","family":"Shimozawa","sequence":"additional","affiliation":[{"name":"Health and Nutrition Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, , 1-1 Hachimandai, Tsukuba, Ibaraki, 305-0843, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiro","family":"Yasutomi","sequence":"additional","affiliation":[{"name":"Health and Nutrition Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, , 1-1 Hachimandai, Tsukuba, Ibaraki, 305-0843, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryotaro","family":"Yabe","sequence":"additional","affiliation":[{"name":"Yamaguchi University Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, , 1677-1 Yoshida, Yamaguchi 753-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Ohama","sequence":"additional","affiliation":[{"name":"Yamaguchi University Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, , 1677-1 Yoshida, Yamaguchi 753-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Sato","sequence":"additional","affiliation":[{"name":"Yamaguchi University Laboratory of Veterinary Pharmacology, Joint Faculty of Veterinary Medicine, , 1677-1 Yoshida, Yamaguchi 753-8515, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"2023053106512523300_ref1","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1146\/annurev-biochem-062917-012332","article-title":"Protein serine\/threonine phosphatases: keys to unlocking regulators and substrates","volume":"87","author":"Brautigan","year":"2018","journal-title":"Annu. Rev. Biochem."},{"key":"2023053106512523300_ref2","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1042\/BST20201313","article-title":"Protein phosphatase 2A (PP2A) mutations in brain function, development, and neurologic disease","volume":"49","author":"Verbinnen","year":"2021","journal-title":"Biochem. Soc. Trans."},{"key":"2023053106512523300_ref3","first-page":"2277","article-title":"To be or not to be: PP2A as a dual player in CNS functions, its role in neurodegeneration, and its interaction with brain insulin signaling","volume":"76","author":"Javadpour","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"2023053106512523300_ref4","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1111\/j.1460-9568.2005.04391.x","article-title":"Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation","volume":"22","author":"Liu","year":"2005","journal-title":"Eur. J. 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