Prion

The history of human prion diseases began with the original description, by Hans Gerhard Creutzfeldt and by Alfons Maria Jakob, of patients with a severe brain disease that included speech abnormalities, confusion, and myoclonus, in a disease that was then named Creutzfeldt Jakob disease (CJD). Later, in Papua New Guinea, a disease characterized by trembling was identified, and given the name "Kuru". Neuropathological examination of the brains from CJD and Kuru patients, and of brains of sheep with scrapie disease revealed significant similarities and suggested a possible common mode of infection that, at the time, was thought to derive from an unknown virus that caused slow infections...

Chronic wasting disease (CWD) is a fatal prion disease of the family Cervidae that circulates in both wild and captive cervid populations. This disease threatens the health and economic viability of the captive cervid industry, which raises cervids in contained spaces for purposes such as hunting and breeding. Given the high transmissibility and long incubation period of CWD, the introduction and propagation of the infectious prion protein within and between captive cervid farms could be devastating to individual facilities and to the industry as a whole...

Prion disease is an infectious and fatal neurodegenerative disease. Western blotting (WB)-based identification of proteinase K (PK)-resistant prion protein (PrPres ) is considered a definitive diagnosis of prion diseases. In this study, we aimed to detect PrPres using formalin-fixed paraffin-embedded (FFPE) specimens from cases of sporadic Creutzfeldt-Jakob disease (sCJD), Gerstmann-Sträussler-Scheinker disease (GSS), glycosylphosphatidylinositol-anchorless prion disease (GPIALP), and V180I CJD. FFPE samples were prepared after formic acid treatment to inactivate infectivity...

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are multifunctional proteins with integral roles in RNA metabolism and the regulation of alternative splicing. These proteins typically contain prion-like domains of low complexity (PrLDs or LCDs) that govern their assembly into either functional or pathological amyloid fibrils. To date, over 60 mutations targeting the LCDs of hnRNPs have been identified and associated with a spectrum of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD)...

Creutzfeldt Jakob Disease (CJD) is a rapidly progressive, fatal neurodegenerative disorder, also known as a subacute spongiform encephalopathy. There are three major subtypes of CJD i.e. Sporadic CJD, which occurs for reasons unbeknown to science (85% of known cases), Genetic or Familial CJD which is characterized by the presence of mutations in the human prion protein (PRNP) gene (10-15% cases) and Iatrogenic CJD that occurs via accidental transmission through medical and surgical procedures (1-2% cases). CJD cases occur globally with 1 case per one million population/year...

Fatal familial insomnia (FFI) is a rare autosomal dominant genetic neurodegenerative disease. Generally, FFI patients will develop rapidly progressive dementia, sleep disturbance, autonomic dysfunction, and so on. Cerebrospinal fluid examination of FFI patients normally shows no obvious abnormalities. Here, we report a young male patient who was diagnosed with FFI during the COVID-19 epidemic. Clinical symptoms include psychobehavioral abnormality, cognitive decline, sleep disturbance, and autonomic dysfunction...

Worldwide, 10-15% human prion disease are genetic and inherited, due to the special mutations or insertions in PRNP gene. Herein, we reported two Chinese patients with rapidly progressive dementia who were referred to the national Creutzfeldt-Jacob disease (CJD) surveillance as suspected CJD. Those two patients displayed sporadic CJD (sCJD)-like clinical phenotype, e.g. rapidly progressive dementia, visional and mental problems, sCJD-associated abnormalities in MRI. A missense mutation was identified in one PRNP allele of these two patients, resulting in a change from serine to asparagine at codon 97 (S97N)...

Gerstmann-Sträussler-Scheinker disease with a Pro-to-Leu substitution at codon 105 in the prion protein gene (GSS-P105L) is a rare variant of human genetic prion disease. Herein, we report the case of a patient with GSS-P105L, who showed serial changes in regional cerebral blood flow (rCBF) on single-photon emission computed tomography (SPECT). A 42-year-old woman, with an affected father presenting with similar symptoms, had a 1-year history of progressive gait disturbance, lower-limb spasticity, and psychiatric symptoms...

The Heidenhain variant Creutzfeldt-Jakob disease (CJD) is characterized by isolated visual symptoms at disease onset, which may mimic numerous ophthalmological disorders. Anti-recoverin autoantibody can be found in patients with autoimmune-related retinopathies. The presence of this antibody with visual symptoms might be confusing in the early stages of the Heidenhain variant CJD. We describe the first case of an anti-recoverin antibody found in the Heidenhain variant CJD who presented with progressive blurred vision then memory deterioration proceeded later...

Prions are misfolded proteins that accumulate within the brain in association with a rare group of fatal and infectious neurological disorders in humans and animals. A current challenge to research is a lack of in vitro model systems that are compatible with a wide range of prion strains, reproduce prion toxicity, and are amenable to genetic manipulations. In an attempt to address this need, here we produced stable cell lines that overexpress different versions of PrPC through lentiviral transduction of immortalized human neural progenitor cells (ReN VM)...

Coronavirus disease 2019 (COVID-19) pandemic has taken the world by a storm, posing a gruelling challenge to the medical fraternity globally. Besides its very high infectivityinfectivity, significant organ dysfunction occurs in critically ill COVID-19 patients, leading to severe morbidity and mortality. Pulmonary involvement is the leading cause of death in these patients to be followed by the cardiovascular involvement. Kidney involvement due to COVID-19 is becoming more discernible with AKI adversely affecting the outcome...

The most common genetic Creutzfeldt-Jakob disease (gCJD) in Japan is caused by a point mutation in which isoleucine replaces valine at codon 180 of the prion protein ( PrP ) gene (V180I gCJD). Evidence suggests that cerebral cortex swelling, which appears as abnormal hyperintensities on diffusion-weighted imaging (DWI), is a characteristic magnetic resonance imaging (MRI) finding of V180I gCJD. However, no study has directly compared the MRI findings between V180I gCJD and sporadic CJD (sCJD). The current study, therefore, aims to clarify the imaging features of V180I gCJD, which would lead to prompt genetic counselling and analysis of the PrP gene, particularly focusing on cerebral cortex swelling...

The crosstalk between viral infections, amyloid formation and neurodegeneration has been discussed with varying intensity since the last century. Several viral proteins are known to be amyloidogenic. Post-acute sequalae (PAS) of viral infections is known for several viruses. SARS-CoV-2 and COVID-19 implicate connections between amyloid formation and severe outcomes in the acute infection, PAS and neurodegenerative diseases. Is the amyloid connection causation or just correlation? In this review we highlight several aspects where amyloids and viruses meet...

Among the transmissible spongiform encephalopathies (TSEs), chronic wasting disease (CWD) in cervids is now a rising concern in wildlife within Europe, after the detection of the first case in Norway in 2016, in a wild reindeer and until June 2022 a total of 34 cases were described in Norway, Sweden and Finland. The definite diagnosis is post-mortem , performed in target areas of the brain and lymph nodes. Samples are first screened using a rapid test and, if positive, confirmed by immunohistochemistry and Western immunoblotting...

Prion diseases are fatal neurologic disorders that can be transmitted by blood transfusion. The route for neuroinvasion following exposure to infected blood is not known. Carotid bodies (CBs) are specialized chemosensitive structures that detect the concentration of blood gasses and provide feedback for the neural control of respiration. Sensory cells of the CB are highly perfused and densely innervated by nerves that are synaptically connected to the brainstem and thoracic spinal cord, known to be areas of early prion deposition following oral infection...

Polymorphism of the prion protein gene ( PRNP ) gene determines an animal's susceptibility to scrapie. Three polymorphisms at codons 136, 154, and 171 have been linked to classical scrapie susceptibility, although many variants of PRNP have been reported. However, no study has investigated scrapie susceptibility in Nigerian sheep from the drier agro-climate zones. In this study, we aimed to identify PRNP polymorphism in nucleotide sequences of 126 Nigerian sheep by comparing them with public available studies on scrapie-affected sheep...

Misfolding of the prion protein is central to prion disease aetiology. Although understanding the dynamics of the native fold helps to decipher the conformational conversion mechanism, a complete depiction of distal but coupled prion protein sites common across species is lacking. To fill this gap, we used normal mode analysis and network analysis to examine a collection of prion protein structures deposited on the protein data bank. Our study identified a core of conserved residues that sustains the connectivity across the C-terminus of the prion protein...

Gerstmann-Sträussler-Scheinker (GSS) disease is an autosomal dominant neurodegenerative disease, and it is characterized by progressive cerebellar ataxia. Up to now, GSS cases with the p.P102L mutation have mainly been reported in Caucasian, but rarely in Asian populations. A 54-year-old female patient presented with an unstable gait in the hospital. Last year, she was unable to walk steadily and occasionally choked, could not even walk independently gradually. After taking her medical history, we found that she was misdiagnosed with schizophrenia before the gait problems...

Although multiple sclerosis (MS) and multiple system atrophy (MSA) are both characterized by impaired oligodendrocytes (OLs), the aetiological relevance remains obscure. Given inherent stressors affecting OLs, the objective of the present study was to discuss the possible role of amyloidogenic evolvability (aEVO) in these conditions. Hypothetically, in aEVO, protofibrils of amyloidogenic proteins (APs), including β-synuclein and β-amyloid, might form in response to diverse stressors in parental brain...

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