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Inhibition of AGEs-RAGE-PP2A Axis Alleviates Cognitive Impairment after Chronic Heart Failure

Shaodong Li1, Linhai Wang2, Junyan Wang3

  • 1The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China. jishaokang19750515@163.com.

Cellular and Molecular Biology (Noisy-Le-Grand, France)
|August 12, 2023
PubMed

Insights

Targeting the AGEs-RAGE-PP2A pathway effectively mitigates cognitive impairment in chronic heart failure mice by reducing brain amyloid-beta and tau pathology.

Area of Science:

  • Neuroscience
  • Cardiology
  • Biochemistry

Background:

  • Chronic heart failure (CHF) is associated with cognitive impairment (CI).
  • The AGEs-RAGE-PP2A signaling axis is implicated in neurodegenerative processes.

Purpose of the Study:

  • To investigate the role of the AGEs-RAGE-PP2A axis in CHF-induced cognitive impairment.
  • To evaluate the therapeutic potential of targeting this axis.

Main Methods:

  • Mice underwent Transverse Aortic Constriction (TAC) to induce CHF.
  • Groups included Sham, TAC, TAC with RAGE deficiency, TAC treated with aminoguanidine (AGEs inhibitor), and TAC treated with FTY720 (PP2A activator).
  • Cardiac function, behavioral tests, brain histology, and protein expression (Aβ, p-tau, apoptosis markers, PP2A) were assessed.

Main Results:

  • Aminoguanidine and RAGE deficiency significantly improved cardiac and cognitive function in TAC mice.
  • FTY720 partially improved cardiac function but significantly improved cognitive function.
  • All interventions reduced brain Aβ and p-tau, modulated apoptosis-related proteins, and upregulated PP2A expression.

Conclusions:

  • Deficiency in AGEs or RAGE, and PP2A activation, attenuate cognitive impairment in CHF mice.
  • These interventions protect brain structure by reducing Aβ, p-tau, and apoptotic protein expression.

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