Research Paper Volume 12, Issue 8 pp 6880—6890
PP2A subunit PPP2R2C is downregulated in the brains of Alzheimer’s transgenic mice
- 1 Shanghai Ruijin Hospital, Shanghai Ruijin Hospital North, Affiliated to Shanghai Jiaotong University School of Medicine, International Laboratory in Hematology, Aging and Cancer, State Key Laboratory of Medical Genomics, Pôle Sino-Français de Recherche en Sciences du Vivant et Génomique, Shanghai, P.R. China
- 2 Shanghai Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China
- 3 Université Côte d’Azur, CNRS, INSERM, IRCAN, Faculty of Medicine, Nice, France
- 4 Department of Genetics, CHU, Nice, France
Received: August 22, 2019 Accepted: March 9, 2020 Published: April 14, 2020https://doi.org/10.18632/aging.103048
How to Cite
Copyright © 2020 Leong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.