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E3 ligases and DUBs target ferroptosis: A potential therapeutic strategy for neurodegenerative diseases.

Linxia Lu1, Cili Jifu1, Jun Xia1

  • 1College of Basic Medicine, Jiamusi University, Jiamusi 154007, People's Republic of China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
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Summary

Ferroptosis, a cell death pathway involving iron and lipid peroxidation, is implicated in neurodegenerative diseases. Targeting the ubiquitin system, including E3 ligases and DUBs, offers new therapeutic strategies for these conditions.

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Deubiquitinating enzymesE3 ubiquitin ligasesFerroptosisTherapy for neurodegenerative diseases

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Ferroptosis is an iron-dependent form of cell death involving lipid peroxidation.
  • Neurodegenerative diseases (NDDs) like Alzheimer's and Parkinson's disease are increasingly linked to ferroptosis.
  • The ubiquitin-proteasome system (UPS) plays a role in regulating cellular processes, including ferroptosis.

Purpose of the Study:

  • To review the mechanisms of ferroptosis and its role in NDDs.
  • To explore the involvement of the ubiquitin system, specifically E3 ligases (E3s) and deubiquitinating enzymes (DUBs), in ferroptosis.
  • To discuss the therapeutic potential of targeting ferroptosis and the ubiquitin system for NDD treatment.

Main Methods:

  • Literature review of studies on ferroptosis, NDDs, and the ubiquitin system.
  • Analysis of the regulatory roles of E3s and DUBs in ferroptosis.
  • Synthesis of current understanding of ferroptosis pathophysiology in NDDs.

Main Results:

  • Ferroptosis is a key mechanism in the pathogenesis of various NDDs.
  • Ubiquitination, mediated by E3s and DUBs, significantly influences ferroptosis sensitivity.
  • Dysregulation of E3s and DUBs is associated with NDD progression.

Conclusions:

  • Targeting ferroptosis and the ubiquitin system presents promising therapeutic avenues for NDDs.
  • E3- and DUB-targeted drugs, alongside ferroptosis inhibitors, could prevent or ameliorate NDD progression.
  • Further research into the ferroptosis-ubiquitin signaling axis is crucial for developing effective NDD treatments.