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. 2024 Dec 10;20(12):e1012676.
doi: 10.1371/journal.ppat.1012676. eCollection 2024 Dec.

Therapeutic perspectives for prion diseases in humans and animals

Rebeca Benavente  1 , Rodrigo Morales  1   2
Affiliations

Therapeutic perspectives for prion diseases in humans and animals

Rebeca Benavente et al. PLoS Pathog. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Dr. Morales listed as an inventor in a patent describing the protein misfolding cyclic amplification (PMCA) technique. Ms. Benavente has no conflicts to disclose.

Figures

Fig 1
Fig 1. PrP-specific therapeutic strategies against prion diseases.
Different strategies have been explored targeting either PrPC or PrPSc. Some approaches have focused in knocking down or capturing PrPC to limit the availability of substrate for the prion protein misfolding process. Other strategies have been used to directly inhibit the PrPC-to-PrPSc conversion process. Additional avenues, either capturing or degrading PrPSc, have also been tested. Along this line, further approaches aim to inhibit the formation of the most deleterious prion particles (e.g., oligomers). Moreover, increasing the degradation of PrPSc aggregates has also been tested. This figure was created using BioRender.
Fig 2
Fig 2. PrP downstream approaches for anti-prion therapies.
The prion misfolding process can be reduced by preventing the localization of the normal prion protein in lipid rafts (one of the hypothesized sites of conversion) through the depletion of cholesterol. Prion toxicity can also be reduced by targeting its extensively described downstream mechanisms, including apoptosis mediated by endoplasmic reticulum or mitochondrial stresses. Attempts to increase the degradation of this protein through autophagy, lysosomal degradation and priming of the immune system have also been explored. Some reports also suggest that the increase of endoplasmic reticulum-associated protein degradation (ERAD) pathways might be beneficial to the degradation of PrPSc. An additional therapeutic option involves the refolding of the prion protein into its native state through chaperones. Finally, the prevention of neurodegeneration by reducing ROS production has also been explored. Some of the drugs tested in different pathways are marked in this figure. This figure was created using BioRender.
See this image and copyright information in PMC

References

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