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Urolithin A Protects Neuronal Cells against Stress Damage and Apoptosis by Atp2a3 Inhibition

Yao Xiao1,2, Kailin Li1, Ji Bian3

  • 1College of Food Science and Engineering, Northwest A & F University, Yangling, Shaanxi, 712100, P. R. China.

Molecular Nutrition & Food Research
|September 5, 2023
PubMed
Abstract

Insights

Urolithin A (UA) alleviates cognitive impairment in type 2 diabetes by reducing neuronal stress and Tau hyperphosphorylation. This neuroprotective effect is mediated by suppressing the Atp2a3 gene, offering a potential therapeutic target for neurodegeneration.

Area of Science:

  • Neuroscience
  • Metabolic Disorders
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and neuronal stress.
  • Endoplasmic reticulum (ER) stress and Tau hyperphosphorylation are implicated in diabetes-associated neurodegeneration.

Purpose of the Study:

  • To investigate the therapeutic potential of Urolithin A (UA) in mitigating cognitive deficits in a T2DM mouse model.
  • To elucidate the underlying mechanisms of UA's neuroprotective effects, focusing on ER stress and related pathways.

Main Methods:

  • A T2DM mouse model was induced using a high-fat diet and streptozotocin.
  • Primary hippocampal neurons and HT22 cells were treated with high glucose or DMNQ to induce stress.
  • UA treatment effects on cognitive function, ER stress markers, Tau hyperphosphorylation, oxidative stress, apoptosis, and Atp2a3 gene expression were assessed.

Main Results:

  • UA treatment attenuated cognitive impairment in T2DM mice, suppressing ER stress and Tau hyperphosphorylation.
  • UA reduced oxidative stress, ER stress, aberrant energy metabolism, and apoptosis in neuronal cells.
  • UA significantly down-regulated Atp2a3 expression, a key regulator of calcium homeostasis and ER stress, in stressed cells.

Conclusions:

  • Urolithin A exhibits neuroprotective effects against diabetes-associated cognitive impairment by suppressing neuronal stress.
  • The mechanism involves the down-regulation of Atp2a3, suggesting its role in UA's therapeutic action.
  • UA represents a promising pharmaceutical target for treating neurodegeneration and stress damage in T2DM.
Keywords:
Atp2a3Urolithin Aapoptosiscognitive impairmentstress damage

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