Prion最新文献

Chronic wasting disease (CWD) is a fatal neurodegenerative prion disease of cervids that can be transmitted through direct physical contact, indirect contact with a contaminated environment, or vertical transmission. CWD is characterized by a long incubation period followed by symptoms like loss of appetite resulting from the destruction of brain tissue. While the consequences for infected animals are clear, a previous study from our laboratory showing lower body weights in the foetuses of CWD-positive female deer suggests those consequences may be intergenerational. In this study, we addressed the impact of maternal CWD infection on foetal head development (as a proxy for brain growth) in wild white-tailed deer using data from CWD management efforts in northern Illinois, U.S.A. Multivariate, multilevel, Bayesian Gamma regression found that maternal CWD infection reduced foetal head nose-occipital length and crown-jaw circumference by 6.76% and frontal-occipital length by 11.31%. These findings suggest impeded brain development in the offspring of CWD-infected female deer, which could reduce fawns' survival and success after birth and lead to a decline in population fitness over time. This study is the first to demonstrate the detrimental effects of a prion disease on foetal brain development in any animal species regardless of whether vertical transmission has occurred.

In memoriam of Pawel P. Liberski, an enthusiastic scientist of rare intelligence, a loyal and generous friend, and a truly vivid personality.

Infectious prions (PrP^Sc) are largely resistant to proteolytic digestion, including proteinase K (PK) digestion. While nucleic acid extracts are generally considered non-infectious from a classical microbiology context (i.e. free of intact bacteria and viruses), we investigated whether standard DNA purification methods co-purify PrP^Sc, posing an unrecognized biosafety risk. Commercial DNA extraction kits can eliminate conventional pathogens but are likely ineffective against PrP^Sc due to resistance to kit reagents and enzymatic degradation. Two laboratories, the University of Minnesota Center for Prion Research and Outreach (MNPRO) and the Canadian Food Inspection Agency (CFIA), independently tested filter-based and magnetic bead-based DNA extraction kits using tissues from chronic wasting disease (CWD)-positive and -negative white-tailed deer (WTD; Odocoileus virginianus), as well as prion-infected and control Syrian hamster (Mesocricetus auratus) brains. CFIA used two filter-based kits (one automated, one manual), while MNPRO tested two manual kits (filter- and magnetic bead-based). PrP^Sc seeding activity was measured in extracted DNA and source tissues using real-time quaking-induced conversion (RT-QuIC). MNPRO found substantial to almost perfect agreement between RT-QuIC seeding activity of DNA eluates from both extraction methods and that of the source WTD tissue homogenate. CFIA optimized RT-QuIC to a 30-hour runtime, achieving 74% sensitivity and 94% specificity in 88 archived WTD DNA samples. Both laboratories concluded that commercial DNA extraction kits do not eliminate PrP^Sc, enabling carry-over into DNA eluates. Until infectivity is resolved by animal bioassay, DNA from PrP^Sc-positive tissues should be handled under biosafety protocols appropriate for the originating prion disease, with decontamination and containment procedures.

Mutations in superoxide dismutase 1 (SOD1) cause paralysis in familial amyotrophic lateral sclerosis and promote its misfolding into neurotoxic aggregates. Previous studies have shown that mice expressing the ALS-causing G85R variant of SOD1 develop paralysis much faster after intraspinal injection of spinal homogenates from paralysed G85R SOD1 mice. These findings, and other studies in cell models, established the prionoid templating properties of misfolded mutant SOD1. Previously, however, we noted that the widely used Gur1-G93A SOD1 mice, which express at high levels and develop paralysis by 6 months of age, were resistant to seeding by homogenates from paralysed G93A mice. A line of G93A mice that expresses at very low levels (VLE-G93A) was responsive to seeding but at low efficiency. The poor susceptibility of G93A-SOD1 mice to seeding was not what we expected if prion-like propagation is essential to SOD1 ALS pathogenesis. In our prior studies, seeding homogenates from paralysed G93A-SOD1 mice were injected into the spine of newborn mice, leading us to question whether older G93A SOD1 mice might be more susceptible to seeding. Here, we establish that adult VLE G93A SOD1 mice (up to 12 months of age) injected intrathecally with seeding homogenates containing misfolded G93A or G85R SOD1 developed accelerated motor neuron disease efficiently. Thus, we demonstrate that both the route and age of inoculation can influence the efficiency of SOD1 seeding to induce motor neuron disease in VLE G93A-SOD1 mice. These data, together with our earlier reports, suggest that prion-like templating contributes to disease progression in SOD1-ALS.

Clinicopathologically, dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) presents as either a non-plaque or plaque type. Here, we report an autopsy case of plaque-type dCJD, supported by genetic and biochemical analyses. A 41-year-old man manifested right-hand paraesthesia. He had received a dural graft in the right parietal region following a traumatic acute subdural haematoma 27 years before symptom onset. The clinical course was slowly progressive. The patient became unable to walk independently 17 months after onset, showed cognitive decline at 22 months, and developed myoclonus and akinetic mutism at 24 months. Periodic sharp-wave complexes were never observed on electroencephalography throughout the disease course. He died 26 months after symptom onset. No mutations were identified in the prion protein (PrP) gene, and the codon 129 polymorphism was homozygous for methionine. Neuropathologically, mild to moderate spongiform changes with fine vacuoles, neuronal loss, and astrogliosis were observed in the brain and spinal cord. Degeneration was relatively severe in the limbic system, striatum, thalamus, and cerebellum, resembling the distribution pattern of VV2 sporadic CJD. Abnormal PrP deposition was broadly distributed consisting of synaptic, perineuronal, and plaque forms. In particular, intense PrP staining was observed throughout the spinal grey matter. Western blotting detected intermediate-type PrP in the brain and cervical cord, but not in systemic organs. Considering the clinical course and PrP staining in the spinal cord, PrP transmission is suggested to occur not directly from the transplanted dura mater to the central nervous system, but rather indirectly via a peripheral route.

Prion 2025, held in Armação dos Búzios, Brazil (3-7 November 2025), was the first PRION congress in Latin America and brought together 260 participants from 22 countries. Building on the broadening scope of recent meetings, this edition placed the cellular prion protein (PrP) back at centre stage while maintaining a strong focus on prion-like mechanisms and functional amyloids. Clinical and epidemiological sessions addressed rapidly progressive dementias and prion and prion-like diseases, underscoring the need for structured diagnostic pathways and closer interaction between surveillance networks and specialized centres. Basic science sessions explored PrP biology, with an emphasis on liquid - liquid-phase separation, early misfolding events, and structural features that underpin prion propagation and strain diversity. The programme also dedicated space to emerging diagnostics and biomarkers, as well as to therapeutic strategies, including PrP-lowering approaches and targeting proteostasis and cellular clearance pathways. Sessions on yeast, bacterial, and memory amyloids broadened the discussion to functional and evolutionary aspects of amyloid formation. Finally, Prion 2025 strengthened engagement with patient organizations and families, incorporating dedicated panels and family-oriented activities into the programme. Overall, the meeting reinforced links between basic and translational prion research and placed patients' and families' perspectives at the heart of the discussion.

Chronic wasting disease (CWD) is a highly contagious prion disease occurring in free-ranging and farmed cervids. In the Republic of Korea, cases of CWD continue to be detected almost annually, on both new and occasionally previously infected farms. CWD-infected animals contaminate soil and other environmental components by shedding prions through their excreta. Since shed prions remain infectious for years in the environment, they can act as infectivity reservoirs facilitating horizontal transmission of CWD. To prevent the further spread of CWD and allow farms to resume operations, control measures on infected farms, including topsoil removal and thorough environmental treatment with 2N NaOH, have been implemented in the Republic of Korea. Restocking remediated farms with cervids was permitted after confirming the absence of prion seeding activity in soil samples using protein misfolding cyclic amplification (PMCA). A total of 215 samples from 18 remediated farms were collected and analysed using PMCA, with only 3 samples from 3 farms displaying prion seeding activity. While the disease control measures effectively eliminated prion seeding activity in CWD-affected farms, CWD recurred at two of the 18 remediated farms 4 to 5 years after restocking animals. It remains unclear whether the recurrence of CWD at the two farms was due to residual prions in the environment after the control measures, or the introduction of the infected animals from other farms. This uncertainty is heightened by the annual occurrence of CWD at multiple farms and the absence of a traceability system for farmed cervids.

Bovine Spongiform Encephalopathy (BSE) is a fatal neurodegenerative disease in cattle which can be either classical BSE (C-BSE) or atypical BSE (including H-BSE and L-BSE). Here, we report the results of our analyses of an H-BSE case found in Canada in 2021, indicating restriction of the pathological agent (PrP^Sc) mainly to the central nervous system with no or occasional weak involvement of peripheral tissues. Importantly, a non-synonymous mutation at codon 211 of the PRNP gene was detected and confirmed to be present as a germline mutation. This is the first case of BSE in Canada with a predisposing E211K mutation.

Background: The prion diseases (PrD) are a group of progressive, fatal, neurodegenerative diseases, for which the Medical Research Council Prion Disease Rating Scale (MRC Scale) can be used to assess patients' functional deterioration. Findings from previous qualitative interviews with caregivers and clinical experts identified potential ambiguities in the scale that could lead to inconsistent scoring within and/or between raters.

Methods: A draft User Guide was developed based on findings from a previous qualitative study. The draft included clarifications regarding domain wording, scoring levels, and guidance for response option selection. Five clinical experts with PrD management experience provided written feedback on the draft User Guide, which was incorporated into a revised User Guide. A 90-minute consensus meeting was then held with these experts to confirm the final content to be included in the User Guide.

Results: The final User Guide was designed to accompany the MRC Scale and assist with rater decisions related to which response option most accurately describes a patient's health status. Conclusions: The User Guide is expected to be a valuable complement to the MRC Scale, which is poised to rise in use and prominence as global clinical research efforts accelerate to address the significant unmet need of PrD patients.

The Prion 2024 annual conference, held in Nanchang, China, from 23 to 27 October, drew nearly 300 leading scientists, clinicians, researchers, and students from 17 countries to examine the latest advancements in prion research and related diseases. This landmark event marked the inaugural international prion conference hosted in a developing nation for the first time and celebrated the 20th anniversary of the NeuroPrion Association, the organizing body of this prestigious annual gathering - 'Celebrating Two Decades of Progress: Pioneering a New Era.' The conference spotlighted key themes such as epidemiology, pathogenesis, the connections between ageing and neurodegenerative diseases. It showcased innovative diagnostic and therapeutic strategies for both human and animal prion diseases, as well as related conditions including Alzheimer's and Parkinson's diseases, prion protein-associated cancers, and renal injury. The programme featured 70 invited talks and 21 selected oral presentations, culminating in 7 plenary sessions led by esteemed speakers, including Nobel Laureate Stanley B. Prusiner. This overview summarizes key presentations and highlights significant aspects of the conference, emphasizing the impactful discussions and collaborations that emerged from this historic event.