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Small Molecules with Anti-Prion Activity.

Carlo Mustazza1, Marco Sbriccoli2, Paola Minosi3

  • 1National Centre for Control and Evaluation of Medicines, Italian National Institute of Health, Viale Regina Elena 299, 00161 Rome, Italy.

Current Medicinal Chemistry
|September 28, 2019
PubMed
Summary
This summary is machine-generated.

Discovering effective treatments for prion diseases remains challenging. This review explores Structure-Activity Relationships (SAR) of anti-prion agents targeting either PrPSc or PrPC, aiming for better therapeutic strategies.

Keywords:
PrionsStructure- Activity Relationship (SAR)amyloidhistological dyesscrapietransmissible spongiform encephalopathies

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Area of Science:

  • Neurodegenerative diseases
  • Prion biology
  • Medicinal chemistry

Background:

  • Prion pathologies are fatal neurodegenerative conditions caused by misfolded prion proteins (PrPSc).
  • Current treatments for prion diseases are limited, with no available cures.
  • Targeting PrPSc directly proved challenging due to prion strain diversity.

Purpose of the Study:

  • To review the Structure-Activity Relationships (SAR) of various chemical classes of anti-prion agents.
  • To explore different therapeutic strategies, including targeting PrPC, metal-mediated oxidation, and indirect cellular mechanisms.
  • To highlight advancements in high-throughput screening for prion-specific agents.

Main Methods:

  • Review of existing literature on anti-prion agents and their SAR.
  • Analysis of different therapeutic targets: PrPSc, PrPC, transition metals, and cellular components like PFAR.
  • Discussion of high-throughput screening methodologies.

Main Results:

  • Shifting focus from PrPSc to PrPC ligands has shown promise.
  • Stabilizing native PrPC or inhibiting PrPC/PrPSc interaction are key strategies.
  • Investigating metal-mediated oxidation and indirect cellular targets offers new avenues.

Conclusions:

  • No single anti-prion agent has yet significantly extended survival in animal models.
  • Understanding SAR is crucial for developing more effective prion disease therapeutics.
  • Future research should focus on novel targets and improved screening techniques.