I sub(2) super(P)P2A regulates p53 and Akt correlatively and leads the neurons to abort apoptosis

• Published in: Neurobiology of aging Vol. 33; no. 2; pp. 254 - 264
• Main Authors: Liu, Gong-Ping, Wei, Wei, Zhou, Xin, Zhang, Yao, Shi, Hai-Hong, Yin, Jun, Yao, Xiu-Qing, Peng, Cai-Xia, Hu, Juan, Wang, Qun, Li, Hong-Lian, Wang, Jian-Zhi
• Format: Journal Article
• Language: English
• Published: 01.02.2012
• ISSN: 0197-4580
• DOI: 10.1016/j.neurobiolaging.2010.01.016

A chronic neuron loss is the cardinal pathology in Alzheimer disease (AD), but it is still not understood why most neurons in AD brain do not accomplish apoptosis even though they are actually exposed to an environment with enriched proapoptotic factors. Protein phosphatase-2A inhibitor-2 (I sub(2) super(P)P2A), an endogenous PP2A inhibitor, is significantly increased in AD brain, but the role of I sub(2) super(P)P2A in AD-like neuron loss is elusive. Here, we show that I sub(2) super(P)P2A regulates p53 and Akt correlatively. The mechanisms involve activated transcription and p38 MAPK activities. More importantly, we demonstrate that the simultaneous activation of Akt induced by I sub(2) super(P)P2A counteracts the hyperactivated p53-induced cell apoptosis. Furthermore, I sub(2) super(P)P2A, p53 and Akt are all elevated in the brain of mouse model and AD patients. Our results suggest that the increased I sub(2) super(P)P2A may trigger apoptosis by p53 upregulation, but due to simultaneous activation of Akt, the neurons are aborted from the apoptotic pathway. This finding contributes to the understanding of why most neurons in AD brain do not undergo apoptosis.