PP2A subunit PPP2R2C is downregulated in the brains of Alzheimer's transgenic mice
PP2A subunit PPP2R2C is downregulated in the brains of Alzheimer's transgenic mice
复制标题
阿尔茨海默病转基因小鼠大脑中 PP2A 亚基 PPP2R2C 下调
DOI：
10.18632/aging.103048
复制
发表时间：
2020-04-30
期刊：
影响因子：
5.2
通讯作者：
Lu, Yiming
中科院分区：
文献类型：
--
作者：
Leong, Waiian;Xu, Wei;Lu, Yiming
PP 2A的靶向表明与tau相关的认知和功能下降密切相关。然而，关于PP 2A亚基的表达和PP 2A活性在AD过程中是如何失调的知之甚少，排除了用于恢复AD患者中PP 2A的任何特异性靶向策略。虽然含有调节亚基PR 55/Bα（由PPP 2 R2 A基因编码）的PP 2A异源三聚体是主要的tau磷酸酶，但其他脑特异性PP 2A调节亚基参与tau去磷酸化仍不清楚。PR 55/Bγ（由PPP 2 R2 C基因编码）是脑中的关键磷酸酶，PPP 2 R2 C的单核苷酸多态性（SNP）与多种精神障碍有关。通过测量PPP 2 R2 C在Wt和转基因AD小鼠中的差异时空表达模式，我们揭示了与Wt小鼠脑相比，PPP 2 R2 C在老年AD小鼠脑中的表达下调。在培养的细胞中，PPP 2 R2 C表达调节PP 2A活性和tau去磷酸化。这些结果表明，PPP 2 R2 C表达的失调可能参与AD的发病，并且特异性靶向PPP 2 R2 C表达或活性是针对脑痴呆病症（包括AD和其他tau蛋白病）的有希望的策略。
Targeting of PP2A suggests a close link to tau-related cognitive and functional declines. However, little is known about how the expression of PP2A subunits and PP2A activity are dysregulated in the course of AD, precluding any specific targeting strategy for restoring PP2A in AD patients. Although the PP2A heterotrimer containing the regulatory subunit PR55/Bα (encoded by the PPP2R2A gene) is the major tau phosphatase, the involvement of other brain-specific PP2A regulatory subunits in tau dephosphorylation remains unknown. PR55/Bγ (encoded by the PPP2R2C gene) is a pivotal phosphatase in the brain, and single-nucleotide polymorphisms (SNPs) of PPP2R2C are involved in several mental disorders. By measuring the differential spatiotemporal expression patterns of PPP2R2C in Wt and transgenic AD mice, we revealed that PPP2R2C expression is downregulated in the aged AD mouse brain as compared to the Wt mouse brain. In cultured cells, PPP2R2C expression regulates PP2A activity and tau dephosphorylation. These results suggest that dysregulation of PPP2R2C expression may be involved in the onset of AD and that specifically targeting PPP2R2C expression or activity is a promising strategy against brain dementia disorders, including AD and other tauopathies.