Age-related alterations in protein phosphatase 2A methylation levels in brains of cynomolgus monkeys: a pilot study
Age-related alterations in protein phosphatase 2A methylation levels in brains of cynomolgus monkeys: a pilot study
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DOI：
10.1093/jb/mvad006
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发表时间：
2023-01-25
影响因子：
2.7
通讯作者：
Sato, Koichi
中科院分区：
文献类型：
--
作者：
Ando, Sana;Sakurai, Masashi;Sato, Koichi
PP2A 是 2A 型丝氨酸/苏氨酸蛋白磷酸酶的主要成员，其异常活性与阿尔茨海默病 (AD) 和路易体痴呆 (DLB) 的发展有关。 PP2A 是一种全酶，催化亚基 PP2Ac 的蛋白质甲基化会改变复杂的组成。据报道，AD 和 DLB 中 PP2Ac 甲基化水平降低。衰老是AD和DLB最常见的危险因素，但衰老与PP2A之间的关系尚未得到详细研究。随着年龄的增长，食蟹猴的 tau 蛋白和 α-突触核蛋白的磷酸化水平会增加。在这项研究中，我们使用分级蛋白研究了 2 至 43 岁猴子大脑中 PP2A 活性调节随衰老的变化。我们发现，细胞质和核可溶部分的 2A 型蛋白磷酸酶活性随着衰老而降低。细胞质和肌氨酰不溶部分中的 PP2Ac 甲基化水平降低。使用细胞质和核可溶部分中的 PP2Ac、去甲基化 PP2Ac 和 PP2A 甲酯酶 PME-1 水平作为属性的主成分分析表明，老年猴子处于同一簇中。我们的研究结果表明，食蟹猴的大脑衰老与PP2A甲基化的变化密切相关。[图表]
The abnormal activity of PP2A, a dominant member of type 2A serine/threonine protein phosphatase, has been implicated in the development of Alzheimer's 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 alpha-synuclein with aging. In this study, we investigated the alterations in the PP2A activity regulation with aging in monkey brains from 2 to 43 years 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.[GRAPHICS]