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Silencing of long noncoding RNA X-inactive specific transcript alleviates Aβ1-42-induced microglia-mediated

Kun-Peng Zhao1, Xin-Yu Wang2, Mei-Qi Shao2

  • 1Department of Geriatric Psychiatry, The Second Affiliated Hospital of Xinxiang Medical University, Henan Mental Hospital, Xinxiang, China.

International Journal of Immunopathology and Pharmacology
|July 4, 2023
PubMed
Abstract

Insights

Long noncoding RNA XIST downregulation alleviates Alzheimer's disease progression by modulating microglial polarization. This process involves the miR-107/PI3K/Akt pathway, reducing neurotoxicity.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline.
  • Microglial activation and neuroinflammation play critical roles in AD pathogenesis.
  • Long noncoding RNAs (lncRNAs) are emerging as key regulators in various diseases, including AD.

Purpose of the Study:

  • To investigate the role of lncRNA XIST in microglial polarization and neurotoxicity in Alzheimer's disease.
  • To elucidate the underlying molecular mechanisms involving microRNA-107 (miR-107) and the PI3K/Akt signaling pathway.

Main Methods:

  • Quantitative real-time PCR to measure XIST and miR-107 levels.
  • Morris water maze test for cognitive function assessment in APP/PS1 mice.
  • Immunohistochemistry, western blot, ELISA, and cell viability assays to evaluate microglial activation, polarization, and neurotoxicity.

Main Results:

  • XIST levels were elevated in APP/PS1 mice, and XIST silencing ameliorated AD progression.
  • XIST knockdown suppressed M1 microglial polarization and pro-inflammatory factors while promoting M2 polarization.
  • XIST silencing reduced Aβ1-42-induced neurotoxicity and apoptosis, potentially via the miR-107/PI3K/Akt pathway.

Conclusions:

  • Downregulation of XIST mitigates Aβ1-42-induced microglia-mediated neurotoxicity in AD.
  • Modulation of microglial M1/M2 polarization by XIST is a key mechanism.
  • The miR-107/PI3K/Akt pathway is implicated in XIST's neuroprotective effects in AD.
Keywords:
Alzheimer’s diseaselong noncoding RNA X-inactive specific transcriptmicroglial polarizationneurotoxicity

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