Recent advances in prion chemotherapeutics

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases with no effective treatments.
• Prion diseases like Creutzfeldt Jakob Disease (CJD), Bovine Spongiform Encephalopathy (BSE), and Chronic Wasting Disease (CWD) pose significant public health concerns.
• The transmissibility of vCJD through blood necessitates effective decontamination and non-toxic therapies.

Purpose of the Study:

• To review current therapeutic strategies for prion diseases.
• To identify promising chemical-based therapeutic targets and drug candidates.
• To update on testing methods and potential synergistic treatment approaches.

Main Methods:

• Focus on chemotherapeutic approaches targeting prion protein (PrP) conversion.
• Investigating compounds that bind PrP(c) or PrP(res), or modulate PrP(c) levels.
• Exploring alternative targets like the laminin receptor and cell signaling molecules.
• Assessing potential neuroprotective agents and combination therapies.

Main Results:

• Chemotherapeutic agents often target the conversion of normal prion protein (PrP(c)) to abnormal (PrP(res)).
• Polyanionic/polycyclic compounds and some polycationic compounds show potential.
• Modulating PrP(c) levels, targeting accessory molecules, and neuroprotection are key strategies.
• Evidence suggests synergistic effects from combining different compounds.

Conclusions:

• Targeting PrP conversion remains a primary therapeutic strategy for prion diseases.
• Diverse chemotherapeutic approaches, including novel targets and combination therapies, show promise.
• Continued research into therapeutic targets and drug candidates is essential for developing effective treatments for TSEs.