Prion Protein (PRNP)
<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Prion Protein</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>PRNP</td>
</tr>
<tr>
<td class="label">Protein Name</td>
<td>Major prion protein (PrP^c)</td>
</tr>
<tr>
<td class="label">Alternative Names</td>
<td>PrP27-30, PrP33-35, CD230</td>
</tr>
<tr>
<td class="label">HGNC ID</td>
<td>HGNC:9444</td>
</tr>
<tr>
<td class="label">Entrez Gene ID</td>
<td>5622</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P04156</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>20p13</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>253 amino acids</td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~33-35 kDa (unglycosylated)</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Type</td>
</tr>
<tr>
<td class="label">Sporadic CJD</td>
<td>Sporadic</td>
</tr>
<tr>
<td class="label">Genetic CJD</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Variant CJD</td>
<td>Acquired</td>
</tr>
<tr>
<td class="label">Fatal Familial Insomnia</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">GSS Syndrome</td>
<td>Genetic</td>
</tr>
<tr>
<td class="label">Kuru</td>
<td>Acquired</td>
</tr>
<tr>
<td class="label">Disease</td>
<td>Species</td>
</tr>
<tr>
<td class="label">Scrapie</td>
<td>Sheep/Goats</td>
</tr>
<tr>
<td class="label">BSE</td>
<td>Cattle</td>
</tr>
<tr>
<td class="label">Chronic Wasting Disease</td>
<td>Deer/Elk</td>
</tr>
<tr>
<td class="label">FSE</td>
<td>Cats</td>
</tr>
<tr>
<td class="label">TME</td>
<td>Mink</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">6 edges</a></td>
</tr>
</table>
Introduction
The prion protein (PrP) represents one of the most fascinating and enigmatic molecules in neurobiology. Encoded by the PRNP gene, this GPI-anchored protein is central to a unique group of neurodegenerative diseases known as transmissible spongiform encephalopathies (TSEs) or prion diseases. Unlike other protein aggregation disorders, prions possess the remarkable ability to transmit their abnormal conformation to normal cellular proteins, creating a self-propagating chain reaction that leads to rapid neurodegeneration. This page provides comprehensive coverage of prion protein structure, function, mechanisms of pathogenesis, disease associations, and therapeutic approaches [@prusiner2023][@aguzzi2009].
Overview
The prion protein (PrP), encoded by the PRNP gene located on chromosome 20p13, is a glycosylphosphatidylinositol (GPI)-anchored protein that plays a central role in prion diseases. Prions are unique among pathogenic agents in that they consist entirely of misfolded protein and lack any nucleic acid component. The normal cellular isoform (PrP^c) is expressed predominantly in the central nervous system but also in peripheral tissues including lymphocytes, cardiomyocytes, and gastrointestinal epithelial cells. The disease-associated scrapie isoform (PrP^Sc) differs from PrP^c primarily in its conformational state, adopting a higher β-sheet content that renders it resistant to proteolysis and capable of forming insoluble aggregates [@caughey2003][@cohen1998].
Prion diseases affect both humans and animals, with manifestations ranging from rapid progressive dementia to cerebellar ataxia. Human prion diseases include Creutzfeldt-Jakob disease (CJD) in its sporadic, familial, and acquired forms, variant CJD (vCJD), fatal familial insomnia (FFI), Gerstmann-Sträussler-Scheinker syndrome (GSS), and kuru. Animal prion diseases include scrapie in sheep and goats, bovine spongiform encephalopathy (BSE), and chronic wasting disease (CWD) in cervids [@collinge2001][@wadsworth2007].
Protein Structure
Domain Architecture
The prion protein contains several distinct structural domains that serve different functions:
N-terminal signal peptide (residues 1-23): Targets the protein to the secretory pathway and is cleaved during post-translational processing
Octarepeat region (residues 51-91): Contains five tandem octapeptide repeats that bind copper ions (Cu^2+) with high affinity
Central hydrophobic region (residues 106-126): Known as the "hydrophobic core," this region is critical for prion formation and contains the sites of several pathogenic mutations
C-terminal globular domain (residues 121-231): Contains the three α-helices and two β-strands that define the protein's tertiary structure
GPI anchor signal sequence (residues 232-253): Directs GPI anchor attachment for membrane localizationThree-Dimensional Structure
The cellular prion protein (PrP^c) adopts a well-defined three-dimensional structure:
- α-helices: Three α-helices are located at residues 144-154 (Helix A), 173-194 (Helix B), and 200-228 (Helix C)
- β-sheets: Two β-strands at residues 128-131 (β1) and 161-164 (β2) form a small β-sheet
- Disulfide bond: A highly conserved disulfide bond connects Helix B and Helix C (Cys179-Cys214)
- Copper binding sites: The octarepeat region coordinates copper ions through histidine residues at positions 69, 76, 84, and 91
- N-linked glycans: Two N-linked glycosylation sites at Asn181 and Asn197
The conversion from PrP^c to PrP^Sc involves a dramatic conformational rearrangement characterized by:
- Loss of α-helical content (from ~40% to less than 10%)
- Increase in β-sheet structure (from less than 10% to over 40%)
- Formation of amyloid fibrils with cross-β structure
- Increased resistance to proteolytic digestion
Prion Strains
One of the most remarkable properties of prions is strain diversity. Multiple distinct disease phenotypes can arise from the same amino acid sequence of PrP. This strain diversity is encoded in the three-dimensional conformation of PrP^Sc, which differs between strains despite identical primary sequences. Strain differences manifest as:
- Variable incubation periods
- Different neuropathological patterns
- Distinct clinical presentations
- Differential patterns of protease resistance
- Species-specific transmission barriers
The mechanism of strain propagation involves the templated conversion of PrP^c adopting the specific conformational template of the infecting PrP^Sc strain [@caughey2018][@soto2011].
Normal Cellular Function (PrP^c)
Despite extensive research, the normal physiological function of PrP^c remains incompletely understood. However, multiple lines of evidence support several important roles:
Synaptic Function and Neuronal Signaling
PrP^c is highly enriched at synaptic terminals, particularly in the presynaptic compartment. Studies using Prnp^0/0 mice (PRNP knockout) have revealed:
- Altered synaptic transmission with impaired long-term potentiation (LTP)
- Reduced neurotransmitter release efficiency
- Abnormalities in synaptic vesicle cycling
- Defects in GABAergic signaling
PrP^c interacts with various synaptic proteins including:
- Synapsin I
- Grb2 and other adaptor proteins
- Neuronal nitric oxide synthase (nNOS)
- Lipid rafts at synaptic membranes
Copper Ion Homeostasis
The octarepeat region of PrP^c binds copper ions (Cu^2+) with high affinity and may function as a copper buffer or sensor. Copper binding is thought to:
- Modulate PrP^c endocytosis and trafficking
- Influence antioxidant enzyme activity
- Regulate copper uptake at the synapse
- Protect against oxidative stress
The relationship between copper and prion disease is complex, as both deficiency and excess of copper can influence disease progression in different contexts [@brown2009].
Neuroprotection and Cell Survival
PrP^c possesses intrinsic neuroprotective properties:
- Anti-apoptotic activity through inhibition of Bax-mediated cell death
- Antioxidant properties via copper-zinc superoxide dismutase (SOD1) activation
- Protection against oxidative stress-induced neuronal damage
- Regulation of autophagy and cellular clearance pathways
Myelin Maintenance and Oligodendrocyte Function
PrP^c is expressed in oligodendrocytes and myelin-producing cells. Studies indicate:
- PrP^c deficiency leads to subtle myelin abnormalities
- Impaired oligodendrocyte maturation in knockout models
- Potential role in maintaining myelin integrity
Cell Adhesion and Signaling
PrP^c interacts with various cell surface molecules and may function as:
- A signaling receptor or co-receptor
- A cell adhesion molecule
- A platform for assembling signaling complexes
Disease Mechanisms (PrP^Sc)
The conversion of normal PrP^c to the disease-associated PrP^Sc isoform initiates a cascade of pathological events:
The templated conversion of PrP^c to PrP^Sc involves:
Direct interaction between PrP^c and PrP^Sc
Structural rearrangement templated by PrP^Sc
Release of newly converted PrP^Sc
Propagation of the conversion cycleThe efficiency of this conversion is influenced by:
- PrP sequence (species-specific differences)
- PrP expression levels
- Cellular factors and chaperones
- Membrane environment and lipid composition
PrP^Sc aggregates manifest as:
- Diffuse synaptic deposits
- Amyloid plaques (in some disease subtypes)
- Spongiform vacuolation
- Astrocytic and microglial activation
The aggregation process involves:
- Nucleation-dependent polymerization
- Formation of oligomeric intermediates
- Maturation into amyloid fibrils
- Interaction with cellular membranes
Neurotoxicity Mechanisms
Multiple pathways contribute to prion-induced neurodegeneration:
- Synaptic dysfunction and loss
- Activation of apoptotic pathways (caspase-dependent and independent)
- Endoplasmic reticulum stress
- Mitochondrial dysfunction
- Oxidative stress and lipid peroxidation
- Excitotoxicity
- [Neuroinflammation](/mechanisms/neuroinflammation)
The "prion toxicity hypothesis" suggests that the intermediate oligomeric species, rather than the mature fibrils, are primarily responsible for neurotoxicity. This concept has therapeutic implications, as targeting these toxic oligomers may be more effective than targeting the end-stage fibrils [@harris2006][@lee2022].
Disease Associations
Human Prion Diseases
Creutzfeldt-Jakob Disease (CJD)
CJD is the most common human prion disease, accounting for approximately 85% of all cases. Three major etiologies are recognized:
- Sporadic CJD (sCJD): Accounts for ~85% of cases with no known cause; typically presents with rapidly progressive dementia, ataxia, myoclonus, and characteristic periodic EEG patterns
- Genetic CJD (gCJD): Associated with pathogenic mutations in PRNP including E200K, D178N, and V210I; represents ~10-15% of cases
- Acquired CJD: Rare, caused by exposure to contaminated tissues (dura mater grafts, growth hormone), or variant CJD from BSE exposure
Variant CJD (vCJD)
Variant CJD emerged in the UK in the 1990s and is causally linked to consumption of BSE-contaminated beef. Key features include:
- Younger age of onset (average ~30 years)
- Prominent psychiatric and behavioral symptoms at onset
- Sensory symptoms and dysesthesias
- Later neurological signs including ataxia and dementia
- Characteristic "florid" PrP plaques in brain tissue
Fatal Familial Insomnia (FFI)
FFI is caused by the D178N mutation with methionine at position 129. It presents with:
- Progressive insomnia and sleep fragmentation
- Autonomic dysfunction (hypertension, tachycardia, hyperhidrosis)
- Motor disturbances including ataxia and dysarthria
- Selective thalamic degeneration
- Cognitive decline in later stages
Gerstmann-Sträussler-Scheinker Syndrome (GSS)
GSS is a rare autosomal dominant disorder associated with PRNP mutations (commonly P102L). Features include:
- Cerebellar ataxia as the presenting symptom
- Slow progression over years to decades
- Cognitive decline in later stages
- Characteristic amyloid plaque pathology
Animal Prion Diseases
Neurodegenerative Overlap
Prion protein interactions are relevant to other neurodegenerative diseases:
- Alzheimer's Disease: PrP^c binds Aβ oligomers and may mediate their synaptic toxicity
- Parkinson's Disease: PrP may modulate α-synuclein aggregation and toxicity
- Amyotrophic Lateral Sclerosis: PrP expression is altered in motor neurons
- Huntington's Disease: PrP interactions with mutant huntingtin
This overlap suggests common mechanisms of protein misfolding and aggregation across neurodegenerative diseases [@rambold2020][@schmitz2020].
Genetic Factors
PRNP Polymorphisms
The polymorphism at codon 129 (methionine vs. valine) profoundly influences prion disease risk:
- Homozygosity (M/M or V/V) is overrepresented in sporadic CJD
- M/M homozygosity is associated with earlier onset in vCJD
- 129 genotype influences clinical phenotype and disease duration
PRNP Mutations
Over 40 pathogenic mutations in PRNP cause familial prion diseases:
- Pathogenic mutations: P102L (GSS), D178N (FFI/gCJD), E200K (gCJD), V180I (gCJD), M232R (gCJD)
- Insertion mutations: Octapeptide repeat insertions cause gCJD
- Penetrance: Variable, with some mutations having incomplete penetrance
Diagnostic Approaches
Clinical Diagnosis
Current diagnostic criteria incorporate:
- Progressive neurological symptoms
- Characteristic neuropsychological profile
- Typical neurological signs (myoclonus, ataxia, cortical blindness)
- Periodic sharp wave complexes on EEG
- Characteristic MRI findings (cortical ribboning, basal ganglia hyperintensities)
Biomarkers
- 14-3-3 protein in cerebrospinal fluid: High sensitivity for CJD
- Total tau: Elevated in CJD vs. other dementias
- Neurofilament light chain (NfL): Raised in prion disease
- Real-time quaking-induced conversion (RT-QuIC): High specificity for PrP^Sc in CSF
Neuropathology
Characteristic findings include:
- Spongiform change (vacuolation)
- Neuronal loss
- Astrocytic gliosis
- PrP deposition (diffuse, synaptic, or plaque-type)
- Kuru-type plaques in vCJD
Therapeutic Approaches
Current Status
No disease-modifying therapies exist for prion diseases. Current management is supportive and symptomatic.
Therapeutic Strategies Under Investigation
Anti-prion compounds: Quinacrine, pentosan polysulfate, chlorpromazine
Immunotherapy: Active and passive immunization approaches
Gene silencing: Antisense oligonucleotides (ASOs) targeting PRNP
Protein stabilization: Small molecules stabilizing PrP^c conformation
Copper chelation: Modulating copper-binding dynamics
Aggregation inhibitors: Targeting toxic oligomer formationClinical Trials
- Multiple Phase I/II trials of quinacrine failed to show efficacy
- ASO-based approaches show promise in preclinical models
- Immunotherapy trials ongoing but challenging due to blood-brain barrier
Challenges
- Rapid disease progression limits therapeutic window
- Blood-brain barrier restricts drug delivery
- Heterogeneity of prion strains complicates targeting
- Lack of validated biomarkers for trial endpoints
Research Models
Animal Models
- Prnp knockout mice: Viable with mild neurological phenotypes
- Transgenic mice: Expressing mutant human PRNP to model disease
- Knock-in mice: Humanized PRNP with disease-causing mutations
- Hamster/sheep models: For studying scrapie and BSE
Cell Culture Models
- Neuronal cell lines: Overexpressing wild-type or mutant PrP
- Induced neurons: From patient-derived iPSCs
- Organotypic slice cultures: For studying prion replication
See Also
- [PRNP Gene](/genes/prnp)
- [Prion Diseases](/diseases/prion-diseases)
- [Creutzfeldt-Jakob Disease](/diseases/creutzfeldt-jakob)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Protein Aggregation](/mechanisms/protein-aggregation)
- [Transmissible Spongiform Encephalopathies](/diseases/tses)
External Links
- [NCBI Gene PRNP](https://www.ncbi.nlm.nih.gov/gene/5622)
- [UniProt PRNP](https://www.uniprot.org/uniprotkb/P04156)
- [OMIM PRNP](https://www.omim.org/entry/176640)
- [Prion Watch](http://prion.s3website.com/)
- [CJD Foundation](https://cjdfoundation.org/)
Epidemiological Considerations
Global Burden
Prion diseases, while individually rare, represent a significant burden on neurological services worldwide. Sporadic CJD affects approximately 1-2 individuals per million population annually, translating to approximately 7,000-14,000 cases globally each year. The disease typically affects individuals between 50-70 years of age, with no significant gender predilection. The sporadic form accounts for the majority of cases (~85%), while genetic prion diseases represent 10-15%, and acquired forms account for less than 1% of all cases.
Risk Factors and Transmission
The understanding of prion disease transmission has evolved significantly over the past three decades. Key transmission routes include:
- Dietary exposure: Consumption of BSE-contaminated beef products led to the vCJD epidemic in the UK
- Iatrogenic transmission: Cases documented from contaminated dura mater grafts, human growth hormone, and corneal transplants
- Blood transfusion: Four cases of vCJD transmission via blood transfusion have been documented
- Genetic susceptibility: Homozygosity at codon 129 and specific PRNP mutations increase susceptibility
The demonstration of asymptomatic carrier states, particularly for vCJD, has raised concerns about potential secondary transmission through medical procedures and blood products. Estimated prevalence of asymptomatic vCJD infection in the UK population is approximately 1 in 2,000, based on tonsillectomy studies [@geschwind2015].
Population Genetics
The PRNP gene shows evidence of balancing selection in human populations, suggesting that prion protein may have provided a selective advantage during evolution. The codon 129 polymorphism represents a classic example of frequency-dependent selection, with both methionine and valine alleles maintained at significant frequencies in all populations studied. This polymorphism may have conferred differential resistance to past prion disease epidemics or other infectious agents.
Molecular Mechanisms of PrP^c to PrP^Sc Conversion
Nucleation-Dependent Polymerization
The conversion of PrP^c to PrP^Sc follows a nucleation-dependent polymerization model:
Lag phase: Stochastic formation of metastable oligomers
Nucleation: Critical oligomers become stable "seeds"
Growth phase: Seeds catalyze conversion of additional PrP^c molecules
Stationary phase: Equilibrium between monomers and polymersThis model explains the long incubation periods in some prion diseases and the observation that disease can be triggered by exposure to pre-formed PrP^Sc seeds.
Template-Directed Misfolding
The conformational conversion involves transfer of structural information from PrP^Sc to PrP^c:
- The β-sheet-rich PrP^Sc template stabilizes similar structures in PrP^c
- Specific interactions between PrP^Sc and PrP^c involve the central region
- Post-translational modifications influence conversion efficiency
- Membrane association may facilitate conversion through lipid interactions
Species Barriers
Transmission between species is typically inefficient due to sequence differences between PrP proteins. The species barrier concept explains:
- Differences in amino acid sequence at key positions
- Conformation compatibility between donor PrP^Sc and host PrP^c
- Requirement for specific structural complementarity
Transgenic mice expressing foreign PrP sequences have demonstrated that species barriers can be overcome through genetic manipulation, confirming the central role of PrP sequence in determining transmission efficiency [@zerr2020][@kunze2022].
Cellular Biology of Prion Diseases
Cellular Entry and Spread
Prion replication occurs primarily within the central nervous system, but initial entry involves:
- Peripheral replication in lymphoid tissues
- Migration via peripheral nerves
- Retrograde transport to the spinal cord
- Subsequent spread throughout the brain
The precise mechanisms of cellular entry and spread remain an area of active investigation, with roles proposed for:
- Cell surface PrP^c interactions
- Receptor-mediated endocytosis
- Tunneling nanotubes between cells
- Extracellular vesicle trafficking
Glial Responses
Prion disease is characterized by prominent astrocytic and microglial activation:
- Reactive astrocytes produce inflammatory cytokines
- Microglial activation accompanies neuronal loss
- Both cell types may contribute to neurotoxicity
- Gliosis correlates with disease progression
Neuroinflammation
Chronic neuroinflammation is a hallmark of prion disease:
- Elevated cytokines including IL-1β, IL-6, TNF-α
- Complement system activation
- Prostaglandin production
- Potential contribution to disease progression
Prevention and Public Health Measures
Infection Control
Standard sterilization procedures are ineffective against prions. Recommended measures include:
- Autoclaving at 134°C for 18+ minutes
- Sodium hydroxide (1N) treatment for 1 hour
- Enhanced precautions for high-risk tissues
- Single-use instruments where possible
Blood Safety
Blood donor deferral policies have been implemented in multiple countries for individuals at risk of vCJD. Pathogen reduction technologies are being developed to inactivate prions in blood products.
Food Safety
BSE surveillance and feed restrictions have dramatically reduced the risk of dietary prion exposure. The experience with the BSE epidemic led to significant changes in food safety regulations worldwide.
Future Directions
Biomarker Development
Reliable biomarkers for early diagnosis and treatment monitoring remain a high priority:
- Blood-based tests for PrP^Sc detection
- Neurofilament light chain as a progression marker
- Imaging biomarkers for prion deposition
- Genetic risk stratification
Therapeutic Development
Several promising approaches are advancing through preclinical and early clinical development:
- ASO-mediated PRNP knock-down showing efficacy in mouse models
- Anti-prion antibodies in development for passive immunization
- Small molecule aggregation inhibitors entering clinical trials
- Gene therapy approaches using viral vectors
Understanding Strain Diversity
Advances in strain typing and characterization will enable:
- Better understanding of genotype-phenotype relationships
- Improved diagnostic specificity
- Development of strain-targeted therapeutics
- Better assessment of transmission risks
Conclusion
The prion protein represents a fascinating example of how a single protein can have dramatically different biological properties depending on its conformational state. The study of prion diseases has revealed fundamental principles of protein misfolding, aggregation, and neurotoxicity that apply broadly to neurodegenerative diseases. While significant challenges remain in developing effective therapies, ongoing research continues to advance our understanding of prion biology and disease mechanisms. The development of biomarkers, therapeutic agents, and preventive strategies offers hope for affected individuals and families.
Additional References
[Collins SJ et al., Epidemiology of CJD (2022)](https://pubmed.ncbi.nlm.nih.gov/34778901/)
[Hill AF & Collinge J, Prion strains and disease phenotypes (2003)](https://pubmed.ncbi.nlm.nih.gov/14578620/)
[Miller MW & CWD in cervids (2020)](https://pubmed.ncbi.nlm.nih.gov/32268422/)
[Brandner S & Jaunmuktane Z, Prion disease pathology (2022)](https://pubmed.ncbi.nlm.nih.gov/35489447/)References
[Unknown, Prusiner SB, Prion Biology and Diseases (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/37254267/)
[Unknown, Aguzzi A & Calella AM, Prions: protein aggregation and beyond (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19543732/)
[Unknown, Caughey B & Lansbury PT, Protofibrils, pores, fibrils, and neurodegeneration (2003) (2003)](https://pubmed.ncbi.nlm.nih.gov/12730368/)
[Unknown, Cohen FE & Prusiner SB, Structural studies of prion proteins (1998) (1998)](https://pubmed.ncbi.nlm.nih.gov/9771754/)
[Unknown, Collinge J, Prion diseases of humans and animals (2001) (2001)](https://pubmed.ncbi.nlm.nih.gov/11255527/)
[Unknown, Wadsworth JDF & Collinge J, Update on human prion disease (2007) (2007)](https://pubmed.ncbi.nlm.nih.gov/17540367/)
[Caughey B et al., Prion protein biology (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29976769/)
[Unknown, Soto C & Castilla J, The dam from prion diseases (2011) (2011)](https://pubmed.ncbi.nlm.nih.gov/21827944/)
[Unknown, Brown DR, The prion protein query (2009) (2009)](https://pubmed.ncbi.nlm.nih.gov/19399618/)
[Unknown, Harris DA & True HL, New insights into prion structure and toxicity (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/17062768/)
[Lee S et al., Neurotoxicity of prion protein (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35604485/)
[Rambold AS et al., Linking prion protein to neurodegeneration (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32360412/)
[Schmitz M et al., Prion diseases and Alzheimer's disease overlap (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32449512/)
[Unknown, Geschwind MD, Prion diseases (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/26052946/)
[Unknown, Zerr I & Hermann P, Diagnostic challenges in CJD (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32070203/)
[Kunze B et al., Antisense therapy for prion disease (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35093418/)
[Miyajima Y et al., Prion protein and copper binding (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34411245/)
[Soto C et al., Prion conversion and aggregation (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32520674/)
[Watzlawik J et al., Prion strains and species barriers (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/33626658/)
[Unknown, Scheckel C & Aguzzi A, Prion pathogenesis and therapeutic strategies (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32015018/)Pathway Diagram
Mermaid diagram (expand to render)