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The search for medications to treat prion diseases has lasted more than 30 years but no clinically validated treatments for prion diseases of humans or livestock have been realized. A primary strategy has been to identify molecules that can inhibit the formation of pathological forms of prion protein, for example, protease-resistant forms called PrP. Such inhibitors can prolong the lives of experimental animals inoculated peripherally with prions, but the practical therapeutic efficacy of known inhibitors against ongoing brain infections has so far been limited by toxicity, insufficient bioavailability to the CNS, and/or strain specificities. Thus, the search continues for clinically applicable inhibitors of PrP accumulation. Here we highlight key cell-free assays that are useful for the initial screening and mechanistic characterization of such compounds and are relatively high throughput, rapid, and cost-effective. These include cell-free conversions, protein misfolding cyclic amplification (PMCA), real time quaking-induced conversion (RT-QuIC), and fluorescence correlation-based competitive binding assays.
This article was published in the following journal.
Name: Current opinion in pharmacology
Transmissible spongiform encephalopathies (TSEs) are a group of lethal neurodegenerative diseases involving the structural conversion of cellular prion protein (PrP) into the pathogenic isoform (PrP) ...
A characteristic feature of transmissible spongiform encephalopathies (TSE) is the progressive accumulation of protein aggregates in the brain in a self-propagation manner. Based on this mechanism, in...
The accumulation of aggregated forms of proteins as toxic species is associated with fatal diseases as amyloid proteinopathies. With the purpose of deconstructing the molecular mechanisms of these typ...
Prion diseases are transmissible neurodegenerative disorders of humans and animals, which are characterized by the aggregation of abnormal prion protein (PrP) in the central nervous system. Although s...
The abnormal assembly of tau, α-synuclein (αSyn), or prion protein into oligomers and multimers underpins the molecular pathogenesis of multiple neurodegenerative diseases. Such pathological aggrega...
PRION-1 aims to assess the activity and safety of Quinacrine (Mepacrine hydrochloride) in human prion disease. It also aims to establish an appropriate framework for the clinical assessmen...
Blood samples collected will be shipped to the sponsor's laboratory to establish analytical performance characteristics of the ADVIA Centaur® Pregnancy Associated Plasma Protein A (PAPP-A...
The purpose of this study to investigate if cases of Creutzfeldt-Jakob Disease (CJD) and other forms of prion disease are being missed in older adults living within Lothian.
The study hypothesis is that that the deleterious effect of prions on the brain may be mediated (at least partially) by activation of serine proteases involved in the coagulation system. I...
This study is designed to better understand the molecular biology of paroxysmal nocturnal hemoglobinuria (PNH) and to determine if prion protein (PrP) functions in long term hematopoietic ...
Rapid methods of measuring the effects of an agent in a biological or chemical assay. The assay usually involves some form of automation or a way to conduct multiple assays at the same time using sample arrays.
Abnormal isoform of prion proteins (PRIONS) resulting from a posttranslational modification of the cellular prion protein (PRPC PROTEINS). PrPSc are disease-specific proteins seen in certain human and animal neurodegenerative diseases (PRION DISEASES).
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks (one of several pseudonyms). These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)
Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Immunoassay - ELISA
Immunoassays are quick and accurate tests to detect specific molecules. Immunoassays rely on an antibody to bind to the specific structure of a molecule. Antibodies are proteins generated by animals in response to the invasion of a foreign molecule (anti...