prion diseases
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2022 ◽  
Vol 55 ◽  
pp. 1-3
Author(s):  
Raquel Sánchez-Valle
Keyword(s):  

Author(s):  
Elisa Uliassi ◽  
Lea Nikolic ◽  
Maria Laura Bolognesi ◽  
Giuseppe Legname

2022 ◽  
Author(s):  
Anirban Basu ◽  
Adil Mahammmad ◽  
Arindam Das

Protein aggregation into oligomeric and fibrillar species are the hallmark of many degenerative diseases like Alzheimer’s and prion diseases, as well as type II diabetes. Compounds that can modulate protein...


2021 ◽  
Vol 102 (12) ◽  
Author(s):  
Kathryn S. Beauchemin ◽  
Judy R. Rees ◽  
Surachai Supattapone

Prion diseases are fatal and infectious neurodegenerative diseases in humans and other mammals caused by templated misfolding of the endogenous prion protein (PrP). Although there is currently no vaccine or therapy against prion disease, several classes of small-molecule compounds have been shown to increase disease-free incubation time in prion-infected mice. An apparent obstacle to effective anti-prion therapy is the emergence of drug-resistant strains during static therapy with either single compounds or multi-drug combination regimens. Here, we treated scrapie-infected mice with dynamic regimens that alternate between different classes of anti-prion drugs. The results show that alternating regimens containing various combinations of Anle138b, IND24 and IND116135 reduce the incidence of combination drug resistance, but do not significantly increase long-term disease-free survival compared to monotherapy. Furthermore, the alternating regimens induced regional vacuolation profiles resembling those generated by a single component of the alternating regimen, suggesting the emergence of strain dominance.


Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2453
Author(s):  
Zoe J. Lambert ◽  
Justin J. Greenlee ◽  
Eric D. Cassmann ◽  
M. Heather West Greenlee

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of neurodegenerative protein misfolding diseases that invariably cause death. TSEs occur when the endogenous cellular prion protein (PrPC) misfolds to form the pathological prion protein (PrPSc), which templates further conversion of PrPC to PrPSc, accumulates, and initiates a cascade of pathologic processes in cells and tissues. Different strains of prion disease within a species are thought to arise from the differential misfolding of the prion protein and have different clinical phenotypes. Different strains of prion disease may also result in differential accumulation of PrPSc in brain regions and tissues of natural hosts. Here, we review differential accumulation that occurs in the retinal ganglion cells, cerebellar cortex and white matter, and plexuses of the enteric nervous system in cattle with bovine spongiform encephalopathy, sheep and goats with scrapie, cervids with chronic wasting disease, and humans with prion diseases. By characterizing TSEs in their natural host, we can better understand the pathogenesis of different prion strains. This information is valuable in the pursuit of evaluating and discovering potential biomarkers and therapeutics for prion diseases.


2021 ◽  
Vol 2086 (1) ◽  
pp. 012117
Author(s):  
N M Melnikova ◽  
M I Sulatsky ◽  
Yu D Diordienko ◽  
A I Sulatskaya

Abstract Ordered protein aggregates, amyloid fibrils, are a marker of many serious diseases, such as Alzheimer’s, Parkinson’s, prion diseases, etc. At present, special attention is paid to the study of external influences that can affect the structure and stability of mature amyloid fibrils, which may be in demand in the development of approaches to the therapy of amyloidosis, as well as in the creation of new high-strength materials on the basis of these protein aggregates. An external factor, the influence of which on fibrils was studied in this work, was temperature denaturation. It was shown that heating lysozyme amyloid fibrils to 60 °C does not lead to their degradation, but leads only to a reversible increase in the intramolecular mobility of amyloid-forming proteins, but does not change their morphology. At the same time, boiling of lysozyme amyloids leads to their irreversible degradation, which occurs at least 5 days after exposure: fibrils that form larger clusters change their secondary structure, and fibrils with a lesser degree of clustering are divided into separate fibers. Obtained data about the factors that change the stability and structure of amyloids can be applied in biotechnology for creating new high-strength nanomaterials on their basis.


PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258682
Author(s):  
Declan Williams ◽  
Mohadeseh Mehrabian ◽  
Hamza Arshad ◽  
Shehab Eid ◽  
Christopher Sackmann ◽  
...  

The prion protein (PrP) is best known for its ability to cause fatal neurodegenerative diseases in humans and animals. Here, we revisited its molecular environment in the brain using a well-developed affinity-capture mass spectrometry workflow that offers robust relative quantitation. The analysis confirmed many previously reported interactions. It also pointed toward a profound enrichment of Na,K-ATPases (NKAs) in proximity to cellular PrP (PrPC). Follow-on work validated the interaction, demonstrated partial co-localization of the ATP1A1 and PrPC, and revealed that cells exposed to cardiac glycoside (CG) inhibitors of NKAs exhibit correlated changes to the steady-state levels of both proteins. Moreover, the presence of PrPC was observed to promote the ion uptake activity of NKAs in a human co-culture paradigm of differentiated neurons and glia cells, and in mouse neuroblastoma cells. Consistent with this finding, changes in the expression of 5’-nucleotidase that manifest in wild-type cells in response to CG exposure can also be observed in untreated PrPC-deficient cells. Finally, the endoproteolytic cleavage of the glial fibrillary acidic protein, a hallmark of late-stage prion disease, can also be induced by CGs, raising the prospect that a loss of NKA activity may contribute to the pathobiology of prion diseases.


2021 ◽  
Author(s):  
Jeong-Min Hong ◽  
Ji-Hong Moon ◽  
Jae-Won Seol ◽  
Sang-Youel Park

Abstract Background: Prion diseases are a group of prevalent and rapidly progressive neurodegenerative disorders that lead to chronic inflammation and neuronal cell death. Calcineurin and autophagy mediate prion-induced neurodegeneration, suggesting that inhibition of calcineurin and autophagy could be a target for therapy. Melatonin has been reported to exert neuroprotective effects against calcium-dependent neuronal cell death.Methods: Real-time quantitative PCR was used to detect mRNA levels of proinflammatory cytokines. Western blot was used to analysis p-nfkb, p-bcl10, calcineurin, prpc and autophagy flux pathway. Immunocytochemistry was used to analysis p-nfkb and calcineurin. Ca2+ levels were measured by fluo-4 using confocal microscope. Calcineurin activity was used to detect with calcineurin cellular activity assay kit. Transmission electron microscopy (TEM) was used to detect autophagy flux.Results: In the present study, we investigated whether melatonin attenuates prion peptide-mediated neuroinflammation and reduces calcineurin. We found that melatonin treatment inhibits prion protein-induced apoptosis. Melatonin inhibited calcium up-regulation and protected the cells against prion peptide‑induced neuron cell death by calcineurin inactivation. Furthermore, melatonin increased p62 protein levels and decrease LC3-II protein levels indicating autophagic flux inhibition and melatonin inhibited prion protein-induced neurotoxicity through autophagy flux inhibition.Conclusions: Taken together, our results illuminate that melatonin attenuated prion protein-induced neurinflammation through calcineurin inactivation and autophagic flux reduction, and also suggest that melatonin may provide effective strategy for therapy against neurodegenerative diseases, including prion diseases.


Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2392
Author(s):  
Laura A. St Clair ◽  
Ali L. Brehm ◽  
Shelby Cagle ◽  
Tillie Dunham ◽  
Jonathan Faris ◽  
...  

Nestled within the Rocky Mountain National Forest, 114 scientists and students gathered at Colorado State University’s Mountain Campus for this year’s 21st annual Rocky Mountain National Virology Association meeting. This 3-day retreat consisted of 31 talks and 30 poster presentations discussing advances in research pertaining to viral and prion diseases. The keynote address provided a timely discussion on zoonotic coronaviruses, lessons learned, and the path forward towards predicting, preparing, and preventing future viral disease outbreaks. Other invited speakers discussed advances in SARS-CoV-2 surveillance, molecular interactions involved in flavivirus genome assembly, evaluation of ethnomedicines for their efficacy against infectious diseases, multi-omic analyses to define risk factors associated with long COVID, the role that interferon lambda plays in control of viral pathogenesis, cell-fusion-dependent pathogenesis of varicella zoster virus, and advances in the development of a vaccine platform against prion diseases. On behalf of the Rocky Mountain Virology Association, this report summarizes select presentations.


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