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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort apoptosis

Gong-Ping Liu1, Wei Wei, Xin Zhou

  • 1Pathophysiology Department, Key Laboratory of Neurological Disease of Education Committee of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.

Neurobiology of Aging
|February 9, 2010
PubMed

Insights

Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)) increases in Alzheimer disease (AD) brains, triggering p53 but also Akt. This Akt activation prevents neuron apoptosis, explaining neuron survival despite pro-apoptotic factors in AD.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Alzheimer disease (AD) is characterized by chronic neuron loss.
  • The precise mechanisms preventing neuron apoptosis in AD, despite pro-apoptotic factors, remain unclear.
  • The role of Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)) in AD-related neurodegeneration is not well understood.

Purpose of the Study:

  • To investigate the role of I(2)(PP2A) in AD-like neuron loss.
  • To elucidate the molecular mechanisms by which I(2)(PP2A) influences neuronal survival pathways.

Main Methods:

  • Analysis of I(2)(PP2A), p53, and Akt levels in AD brains and mouse models.
  • Investigating the interplay between I(2)(PP2A), p53, Akt, and MAPK signaling pathways.
  • Assessing the impact of I(2)(PP2A) on neuronal apoptosis.

Main Results:

  • I(2)(PP2A) levels are elevated in AD brains and mouse models.
  • I(2)(PP2A) positively regulates both p53 and Akt pathways via transcription and p38 MAPK.
  • Simultaneous activation of Akt by I(2)(PP2A) counteracts p53-induced apoptosis, preventing neuron death.

Conclusions:

  • Increased I(2)(PP2A) in AD may initiate apoptosis through p53 upregulation.
  • However, concurrent Akt activation by I(2)(PP2A) aborts the apoptotic pathway, leading to neuron survival.
  • This dual action of I(2)(PP2A) contributes to understanding why neurons persist despite the AD environment.

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