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Updated: May 27, 2025

Quantitative 3D In Silico Modeling q3DISM of Cerebral Amyloid-beta Phagocytosis in Rodent Models of Alzheimer's Disease
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Unveiling the role of KLF9-mediated IFITM3 regulation in amyloidogenesis

Yijia Feng1,2,3, Qian Zhou4, Bolang Hu1,2,3

  • 1Center for Geriatric Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|February 15, 2025
PubMed

Insights

Krüppel-like factor 9 (KLF9) upregulates Interferon-induced transmembrane protein 3 (IFITM3) expression, increasing amyloid-beta (Aβ) production in Alzheimer

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Interferon-induced transmembrane protein 3 (IFITM3) is linked to Alzheimer's Disease (AD) pathogenesis.
  • IFITM3 influences gamma-secretase activity and amyloid-beta (Aβ) generation.
  • Mechanisms regulating IFITM3 gene expression in AD are not fully understood.

Purpose of the Study:

  • To investigate the regulation of IFITM3 gene expression.
  • To elucidate the role of IFITM3 in amyloidogenesis.
  • To identify regulatory factors of IFITM3.

Main Methods:

  • Luciferase assays to identify the IFITM3 promoter region.
  • Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) to detect transcription factor binding.
  • In vitro and in vivo studies using KLF9 overexpression and knockdown models.
  • Aβ quantification in mouse hippocampus.

Main Results:

  • A functional promoter for IFITM3 was identified within its 5'-flanking region.
  • Krüppel-like factor 9 (KLF9) binds to a specific site on the IFITM3 promoter.
  • KLF9 overexpression increases IFITM3 expression and Aβ production in vitro and in vivo.
  • Reduced IFITM3 expression leads to decreased Aβ production.

Conclusions:

  • KLF9 is a key regulator of IFITM3 gene expression.
  • KLF9-mediated IFITM3 upregulation promotes Aβ production, contributing to AD pathogenesis.
  • Inhibiting KLF9-driven IFITM3 expression presents a potential therapeutic strategy for AD by reducing Aβ levels.
Keywords:
Alzheimer's diseaseAβIFITM3KLF9transcriptional regulation

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