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Homocysteine-Responsive Covalent Organic Frameworks as Signaling Scaffolds: Modulating Transsulfuration for

Jialu Zhuang1, Hao Zhang1, Danyou Hu2

  • 1Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Inflammation and Immune-Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei, 230032, China.

Small (Weinheim an Der Bergstrasse, Germany)
|April 17, 2025
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Summary

This study introduces novel homocysteine-responsive covalent organic frameworks (COFs) for depression treatment. These COFs effectively clear homocysteine, reduce neuroinflammation, and improve depressive behaviors in mice.

Keywords:
covalent organic frameworks (COFs)depressionhomocysteinesocial defeat stressstimulus‐responsive materials

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Area of Science:

  • Biomedical Engineering
  • Materials Science
  • Neuroscience

Background:

  • Depression is a major global health issue with inadequate treatments.
  • Elevated homocysteine levels exacerbate depression by increasing neuroinflammation.

Purpose of the Study:

  • To develop novel homocysteine-responsive covalent organic frameworks (COFs) as therapeutic agents for depression.
  • To investigate the mechanisms by which these COFs treat depression.

Main Methods:

  • Synthesized a library of 20 COFs using Schiff-base condensation reactions.
  • Validated COF efficacy using patient serum and a mouse model of depression.
  • Employed metabolomics and transcriptomics to elucidate COF mechanisms.

Main Results:

  • COFs efficiently scavenged homocysteine both exogenously and by enhancing endogenous pathways.
  • COFs reduced neuroinflammation, oxidative stress, and modulated neuronal/microglial activity.
  • COFs improved anxiety and depressive behaviors in mice by preserving mitochondrial function and activating key signaling pathways.

Conclusions:

  • Homocysteine-responsive COFs represent a pioneering therapeutic strategy for depression.
  • These COFs offer significant potential for biomedical applications in treating neurological disorders.