AI Article Synopsis
- Prion diseases involve the transformation of a normal protein (PrP(C)) into a harmful form (PrP(Sc)) in the brain, leading to neurological issues.
- Research indicates that a specific recombinant form of the human prion protein (rHuPrP23-231) can effectively inhibit the spread of both human and mouse prions by binding to PrP(Sc) and preventing its harmful interactions with PrP(C).
- This discovery holds potential for developing new treatments for prion diseases by using a patient's modified prion protein to suppress disease progression without triggering harmful immune responses.
Article Abstract
Prion diseases are associated with the conformational conversion of the cellular prion protein (PrP(C)) into the pathological scrapie isoform (PrP(Sc)) in the brain. Both the in vivo and in vitro conversion of PrP(C) into PrP(Sc) is significantly inhibited by differences in amino acid sequence between the two molecules. Using protein misfolding cyclic amplification (PMCA), we now report that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion propagation in a scrapie-infected mouse cell line. Notably, it binds to PrP(Sc), but not PrP(C), suggesting that the inhibitory effect of recombinant PrP results from blocking the interaction of brain PrP(C) with PrP(Sc). Our findings suggest a new avenue for treating prion diseases, in which a patient's own unglycosylated and anchorless PrP is used to inhibit PrP(Sc) propagation without inducing immune response side effects.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793212 | PMC |
| http://dx.doi.org/10.1038/srep02911 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Exposed Hsp70-binding site impacts yeast Sup35 prion disaggregation and propagation.
Proc Natl Acad Sci U S A
December 2024
Laboratory for Protein Conformation Diseases, RIKEN Center for Brain Science, Wako, Saitama 351-0198, Japan.
The dynamic balance between formation and disaggregation of amyloid fibrils is associated with many neurodegenerative diseases. Multiple chaperones interact with and disaggregate amyloid fibrils, which impacts amyloid propagation and cellular phenotypes. However, it remains poorly understood whether and how site-specific binding of chaperones to amyloids facilitates the concerted disaggregation process and modulates physiological consequences in vivo.
View Article and Find Full Text PDFUnlabelled: The misfolding, aggregation, and the seeded spread of alpha synuclein (α-Syn) aggregates are linked to the pathogenesis of various neurodegenerative diseases, including Parkinson's disease (PD). Understanding the mechanisms by which chaperone proteins prevent the production and seeding of α-Syn aggregates is crucial for developing effective therapeutic leads for tackling neurodegenerative diseases. We show that a catalytically inactive variant of the chaperone HtrA1 (HtrA1*) effectively inhibits both α-Syn monomer aggregation and templated fibril seeding, and demonstrate that this inhibition is mediated by synergistic interactions between its PDZ and Protease domains and α-Syn.
View Article and Find Full Text PDFSupportive care or exhausted neglect: the role of microglia at the end stage of prion disease.
J Clin Invest
December 2024
The transmissible nature of prion diseases enables reproduction of neurodegeneration in small animal models that faithfully follows the disease process observed in the natural disease of animals and humans. This allows the temporal development of disease to be investigated and correlated with pathology in a complex brain environment. In this issue of the JCI, Makarava et al.
View Article and Find Full Text PDFSeeding activity of skin misfolded tau as a biomarker for tauopathies.
Mol Neurodegener
November 2024
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Article Synopsis
- * A study used a seed-amplification assay (SAA) with real-time quaking-induced conversion to detect tau protein activity in the skin of deceased and living patients with tauopathies, showing promising results.
- * The skin tau-SAA exhibited high sensitivity (75-80%) and specificity (95-100%) in diagnosing tauopathies, suggesting that skin samples could be a valuable diagnostic tool in identifying these conditions.
Prion-like Spreading of Disease in TDP-43 Proteinopathies.
Brain Sci
November 2024
Department of Life Sciences, University of Trieste, Via A. Valerio, 28, 34127 Trieste, Italy.
TDP-43 is a ubiquitous nuclear protein that plays a central role in neurodegenerative disorders collectively known as TDP-43 proteinopathies. Under physiological conditions, TDP-43 is primarily localized to the nucleus, but in its pathological form it aggregates in the cytoplasm, contributing to neuronal death. Given its association with numerous diseases, particularly ALS and FTLD, the mechanisms underlying TDP-43 aggregation and its impact on neuronal function have been extensively investigated.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!