Prion protein — mediator of toxicity in multiple proteinopathies

  title={Prion protein — mediator of toxicity in multiple proteinopathies},
  author={Jacob I. Ayers and Stanley B. Prusiner},
  journal={Nature Reviews Neurology},
A new study shows that interactions of the cellular prion protein with amyloid-β, tau and α-synuclein oligomers are important in mediating the toxicity of these proteins in Alzheimer disease and Parkinson disease. The findings suggest a shared pathway that could be a therapeutic target common to multiple neurodegenerative diseases. 
2 Citations
Collusion of α-Synuclein and Aβ aggravating co-morbidities in a novel prion-type mouse model
Novel and unexpected interplays between α-synuclein pathology, Aβ and neuroinflammation in mice that recapitulate the pathology of Alzheimer’s disease and Lewy body dementia are revealed. Expand
Challenges and Advances in Antemortem Diagnosis of Human Transmissible Spongiform Encephalopathies
The RT-QuIC assay stands out for its ability to detect PrPSc in cerebrospinal fluid, olfactory mucosa, and dermatome skin samples with high sensitivity and specificity, and the techniques employed for definite diagnosis, as well as the clinical and paraclinical methods for possible and probable diagnosis. Expand


Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Findings in other neurodegenerative diseases indicate that a broadly similar process of neuronal dysfunction is induced by diffusible oligomers of misfolded proteins. Expand
PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins
It is demonstrated that soluble aggregates of α-synuclein and tau bind to plate-immobilized PrP in vitro and on mouse cortical neurons, and that this binding requires at least one of the same N-terminal sites at which soluble Aβ aggregates bind. Expand
A Unifying Role for Prions in Neurodegenerative Diseases
There has been renewed interest in the possibility that the proteins causing neurodegeneration are all prions, which would profoundly influence the development of diagnostics and effective therapies. Expand
Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance
Findings clarify the relative contributions of previously reported Aβ receptors under controlled conditions and highlight the prominence of PrPC as an Aβ-binding site. Expand
Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy
Two new polymorphic atomic structures of alpha-synuclein fibrils are reported, termed polymorphs 2a and 2b, at 3.0 Å and 3.4 Å resolution, which show a radically different structure compared to previously reported polymorphs. Expand
Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein
Transmembrane PSD proteins heterologously screened for the ability to couple Aβo-PrP(C) with Fyn and found coexpression of the metabotropic glutamate receptor, mGluR5, allowed PrP (C)-bound A βo to activate Fyn. Expand
Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases
Cryo- and immuno- electron microscopy is used to characterise tau filaments that were assembled from recombinant full-length human tau with four or three microtubule-binding repeats in the presence of heparin, illustrating the structural versatility of amyloid filaments and raising questions about the relevance of in vitro assembly. Expand
Antisense oligonucleotides extend survival of prion-infected mice
PrP lowering is the mechanism of action of AsOs effective against prion disease in vivo, and infrequent — or even single — bolus injections of ASOs can slow prion neuropathogenesis and markedly extend survival, even when initiated near clinical signs. Expand
Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy
It is proposed that PrPTME conformation could play a role in targeting TME strains to different neuron populations in which strain-specific formation occurs and is consistent with the idea thatPrPTME protein structure determines the molecular basis of strain variation. Expand
Intracerebral Infusion of Antisense Oligonucleotides Into Prion-infected Mice
Whether ASOs can be used to develop an effective therapy for patients dying of Creutzfeldt–Jakob disease remains to be established. Expand