Sunday, December 7, 2014

Scientific update on the potential for transmissibility of non-prion protein misfolding diseases PRIONOIDS

TECHNICAL REPORT Annual report of the Scientific Network on BSE-TSE 20131 European Food Safety Authority2, 3 European Food Safety Authority (EFSA), Parma, Italy

 

EFSA supporting publication 2013:EN-532 7

 

Scientific update on the potential for transmissibility of non-prion protein misfolding diseases

 

The representative from Austria updated the participants on scientific issues related to the prion-like behaviour of altered proteins (‘prionoids’). The state of the art of experimental and epidemiological evidence on the potential for transmissibility of non-TSE protein misfolding diseases was presented. Experimental evidence shows that there are proteins (e.g. Abeta amyloid, tau, alpha-synuclein) that can behave in a similar way to the prion protein in terms of in-vivo propagation when experimentally inoculated animal models. There is no epidemiological evidence that human to human transmission has occurred in cases other than prion disorders. Still, it is acknowledged that the epidemiological investigation of the occurrence of this hypothetical phenomenon is not straight forward.

 


 

Self-Propagative Replication of Ab Oligomers Suggests Potential Transmissibility in Alzheimer Disease

 

Received July 24, 2014; Accepted September 16, 2014; Published November 3, 2014

 


 

Singeltary comment ;

 


 

Nature Immunology | Article

 

The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation

 

Bernardo S Franklin, Lukas Bossaller, Dominic De Nardo, Jacqueline M Ratter, Andrea Stutz, Gudrun Engels, Christoph Brenker, Mark Nordhoff, Sandra R Mirandola, Ashraf Al-Amoudi, Matthew S Mangan, Sebastian Zimmer, Brian G Monks, Martin Fricke, Reinhold E Schmidt, Terje Espevik, Bernadette Jones, Andrew G Jarnicki, Philip M Hansbro, Patricia Busto, Ann Marshak-Rothstein, Simone Hornemann, Adriano Aguzzi, Wolfgang Kastenmüller & Eicke Latz Affiliations Contributions Corresponding author Nature Immunology 15, 727–737 (2014) doi:10.1038/ni.2913 Received 31 March 2014 Accepted 01 May 2014 Published online 22 June 2014

 

Abstract

 

Microbes or danger signals trigger inflammasome sensors, which induce polymerization of the adaptor ASC and the assembly of ASC specks. ASC specks recruit and activate caspase-1, which induces maturation of the cytokine interleukin 1β (IL-1β) and pyroptotic cell death. Here we found that after pyroptosis, ASC specks accumulated in the extracellular space, where they promoted further maturation of IL-1β. In addition, phagocytosis of ASC specks by macrophages induced lysosomal damage and nucleation of soluble ASC, as well as activation of IL-1β in recipient cells. ASC specks appeared in bodily fluids from inflamed tissues, and autoantibodies to ASC specks developed in patients and mice with autoimmune pathologies. Together these findings reveal extracellular functions of ASC specks and a previously unknown form of cell-to-cell communication.

 


 

This low rate of transmission may be due to low levels of PrPres in the brain homogenates that were inoculated, or it could be that the PrP genotype plays a role in transmission of disease.

 

Prion disease propagation involves the aggregation of abnormal PrP that acts as a template for further aggregation within the brain, a process termed seeding (21,22). The spread of PrP within the brain appears to occur in cell-to-cell fashion in well-defined neuroanatomic pathways (23), the mechanisms of which are yet to be elucidated despite extensive studies. Prion diseases have the potential to be transmissible between persons, a fact that raises public health concerns, particularly regarding vCJD. Assessing the risk for transmission is a challenge because of the varied nature of prion diseases and conflicting evidence over the mechanisms of transmission. Risk assessment is made even more complicated by the existence of prion disease models in which negligible amounts of PrPres are associated with high infectivity titers in vivo (24) and also of models in which PrPres in the form of amyloid plaques develops in the absence of clinical disease or spongiform changes (25).

 

It could be argued that the observation of small plaque-like amyloid deposits in the brains of mice with no neurologic signs of disease after the inoculation of brain homogenates prepared from patients with VPSPr does not indicate disease transmission. Instead, the deposits could indicate an amyloid seeding phenomenon akin to that observed following the experimental inoculation of primates with brain tissue from patients with Alzheimer disease (26). In those experiments, amyloid β seeding occurred in the primate brain in the absence of any clinical signs. Precedence of this phenomenon in prion disease has been set by Piccardo et al. (27), who showed similar results in a mouse model system of prion disease transmission. However, in our study, the brain of 1 mouse exhibited intensely stained, small, round granules within the hippocampus in addition to the plaque-like deposits (Figure 4). These small granules are reminiscent of the microplaques found in brain tissue of humans with VPSPr (4,5). Furthermore, with 4 PrP antibodies, the microplaque deposits in the mouse brain showed the same pattern of differential immunoreactivity as that in the brain of patients with VPSPr (5,6,17). Moreover astrocytosis in the vicinity of the microplaques was also observed in this mouse (Figure 5). This type of astrocytic response is observed in all our model systems of transmissible prion disease, but is absent from the nontransmissible forms of PrP (i.e., amyloid plaques in absence of clinical disease), suggesting that this single mouse may represent a transmission of infection rather than a consequence of seeding of inoculum (25,28). Second passage in the same mouse line will be required to prove this interpretation, but such a study will take an additional 3 years to complete. Although understanding the mechanisms of transmission is an interesting facet of this study, our primary finding is that VPSPr is capable of transmission to transgenic mice expressing PrP, albeit at extremely low levels compared with those of other transmissible prion diseases (e.g., sCJD and vCJD). We demonstrate that VPSPr is a disease with biological properties distinct from those of sCJD and with a limited, but not negligible, potential for infectivity. These results demonstrate the importance of continuing surveillance to fully uncover the growing spectrum of human prion diseases.

 


 

>>> We demonstrate that VPSPr is a disease with biological properties distinct from those of sCJD and with a limited, but not negligible, potential for infectivity. These results demonstrate the importance of continuing surveillance to fully uncover the growing spectrum of human prion diseases.<<<

 

Friday, January 10, 2014

 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 


 

Monday, November 3, 2014

 

*** The prion protein protease sensitivity, stability and seeding activity in variably protease sensitive prionopathy brain tissue suggests molecular overlaps with sporadic Creutzfeldt-Jakob disease

 

Sunday, November 23, 2014

 

Transmission Characteristics of Variably Protease-Sensitive Prionopathy

 

* We concluded that VPSPr is transmissible; thus, it is an authentic prion disease.

 


 


 

Sunday, November 23, 2014

 

Transmission Characteristics of Variably Protease-Sensitive Prionopathy

 

* We concluded that VPSPr is transmissible; thus, it is an authentic prion disease.

 


 

Friday, January 10, 2014

 

vpspr, sgss, sffi, TSE, an iatrogenic by-product of gss, ffi, familial type prion disease, what it ???

 


 


 

Monday, November 17, 2014

 

Prion-like transmission and spreading of tau pathology

 


 

Saturday, February 16, 2013

 

Prions, prionoids and pathogenic proteins in Alzheimer disease

 


 


 

Monday, September 26, 2011

 

Variably Protease-Sensitive Prionopathy, Prionpathy, Prionopathy, FFI, GSS, gCJD, hvCJD, sCJD, TSE, PRION, update 2011

 


 

 Are some commoner types of neurodegenerative disease (including Alzheimer's disease and Parkinson's disease) also transmissible? Some recent scientific research has suggested this possibility

 

 Wednesday, September 21, 2011

 

 PrioNet Canada researchers in Vancouver confirm prion-like properties in Amyotrophic Lateral Sclerosis (ALS)

 

 Researchers’ Discovery May Revolutionize Treatment of ALS

 


 

 Friday, September 3, 2010

 

 Alzheimer's, Autism, Amyotrophic Lateral Sclerosis, Parkinson's, Prionoids, Prionpathy, Prionopathy, TSE

 


 

Sunday, November 23, 2014

 

Confirmed Variant Creutzfeldt-Jakob Disease (variant CJD) Case in Texas in June 2014 confirmed as USA case NOT European

 

‘’The specific overseas country where this patient’s infection occurred is less clear largely because the investigation did not definitely link him to a country where other known vCJD cases likely had been infected.’’

 


 

Friday, December 5, 2014

 

SPECIAL ALERT The OIE recommends strengthening animal disease surveillance worldwide

 

OIE BSE TSE PRION AKA MAD COW DISEASE ?

 

‘’the silence was deafening’’ ...tss

 


 

Saturday, December 6, 2014

 

Detection of Bovine Central Nervous System Tissues in Rendered Animal By-Products by One-Step Real-Time Reverse Transcription PCR Assay

 


 


 


 


 


 


 


 


 


 


 


 


 

 

TSS

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