PrP^C Specific Neutra™ Antibody Products

Are prolonged drug development timelines or challenges in targeting prion protein (PrP^C) misfolding hindering your progress? Creative Biolabs' PrP^C-specific Neutra™ antibody products deliver high-affinity, conformation-specific antibodies engineered through advanced phage display and epitope mapping technologies, enabling precise detection of pathological PrP^C isoforms and accelerating therapeutic discovery for prion-related disorders.

Introduction to PrP^C

PrP^C is a glycophosphatidylinositol (GPI)-anchored cell surface protein predominantly expressed in neuronal tissues. While its physiological role remains incompletely understood, PrP^C is implicated in copper homeostasis, neuroprotection, and synaptic plasticity. Pathologically, misfolded PrP^C (PrP^Sc) undergoes conformational changes, forming β-sheet-rich aggregates responsible for transmissible spongiform encephalopathies (TSEs). The PrP^C-to-PrP^Sc conversion process is central to prion disease pathogenesis, making PrP^C a critical therapeutic and diagnostic target.

• Structural Insights

PrP^C comprises a disordered N-terminal domain and a globular C-terminal domain with three α-helices and two short β-strands. A disulfide bond stabilizes the C-terminal structure, while the N-terminal octapeptide repeats bind copper ions. PrP^Sc, in contrast, exhibits increased β-sheet content, forming amyloid fibrils resistant to proteolysis. Structural studies highlight the α-helical-to-β-sheet transition as the molecular hallmark of prion propagation, underscoring the need for antibodies targeting conformationally sensitive epitopes.

Fig.1 Structural organization of PrP^C.^1,3

• Signaling Pathways

PrP^C interacts with stress-inducible protein 1 (STI1), activating the ERK1/2 and PI3K/Akt pathways to promote neuronal survival. Dysregulated PrP^Sc aggregation disrupts calcium homeostasis, induces endoplasmic reticulum stress, and activates caspase-mediated apoptosis. Additionally, PrP^C modulates NMDA receptor activity, influencing glutamatergic signaling and synaptic integrity—processes compromised in TSEs.

• Associated Diseases

PrP^C misfolding underlies fatal neurodegenerative disorders, including Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker syndrome (GSS). These TSEs are characterized by rapid cognitive decline, motor dysfunction, and neuropathological hallmarks such as spongiform degeneration and amyloid plaque deposition.

Fig.2 The molecular events of PrP^C-ligand interaction in Alzheimer's disease (AD).^2,3

Applications of PrP^C Neutralizing Antibodies

• Therapeutic Intervention in Prion Diseases

Neutralizing antibodies targeting PrP^Sc epitopes block template-driven misfolding, reducing amyloid burden in preclinical models. Intraperitoneal or intracerebral administration of these antibodies delays disease onset and prolongs survival in TSE-infected rodents, demonstrating translational potential.

• Diagnostic Tool Development

PrP^C-specific antibodies allow ultrasensitive detection of PrP^Sc in cerebrospinal fluid (CSF) or blood using QuIC (quaking-induced conversion) assays. Early diagnosis facilitates timely intervention, critical for clinical trials targeting asymptomatic carriers of pathogenic PRNP mutations.

• Mechanistic Studies of Prion Propagation

Antibodies engineered to stabilize native PrP^C conformations unravel the molecular dynamics of misfolding. Applications include fluorescence polarization assays to monitor real-time conformational shifts and cryo-EM studies resolving PrP^Sc fibril architectures.

• Vaccine and Antiviral Strategy Evaluation

Anti-PrP^C antibodies serve as surrogates for evaluating immunotherapies. Passive immunization studies in transgenic mouse models validate efficacy, while epitope mapping guides the design of PRNP-targeted vaccines to induce endogenous neutralizing antibody responses.

Anti-PrP^C Antibodies

Creative Biolabs provides PrP^C-specific Neutra™ antibody products combining unparalleled specificity for pathological prion isoforms with robust validation across translational research applications. Leverage our expertise to overcome challenges in prion disease diagnostics, therapeutics, and mechanistic research. Our PrP^C-Specific Antibodies are engineered to distinguish pathological PrP^Sc from native PrP^C, enabling:

- Epitope-specific binding: Target β-sheet-rich regions or GPI-anchor-proximal domains to block prion propagation.

- High conformational sensitivity: Detect oligomeric intermediates critical for early disease diagnosis.

- Functional neutralization: Inhibit PrP^C-to-PrP^Sc conversion in cellular and animal models, validated through ELISA, immunohistochemistry (IHC), and surface plasmon resonance (SPR).

These antibodies support critical applications in drug screening, biomarker validation, and mechanistic studies of prion aggregation.

PrP^Sc Contact us today to discuss your project requirements and explore tailored solutions for your needs.

REFERENCES

1. Wulf, Marie-Angela, Assunta Senatore, and Adriano Aguzzi. "The biological function of the cellular prion protein: an update." BMC biology 15.1 (2017): 34. https://doi.org/10.1186/s12915-017-0375-5
2. Miranzadeh Mahabadi, Hajar, and Changiz Taghibiglou. "Cellular prion protein (PrP^C): putative interacting partners and consequences of the interaction." International journal of molecular sciences 21.19 (2020): 7058. https://doi.org/10.3390/ijms21197058
3. Distributed under Open Access license CC BY 4.0, without modification.