The misfolding of the α-helical cellular prion protein into a self-propagating β-rich aggregated form is a key pathogenic event in fatal and transmissible neurodegenerative diseases collectively known as prion diseases. Herein, we utilize the interfacial properties of liquid crystals (LCs) to monitor the lipid-membrane-induced conformational switching of prion protein (PrP) into β-rich amyloid fibrils. The lipid-induced conformational switching resulting in aggregation occurs at the nanomolar protein concentration and is primarily mediated by electrostatic interactions between PrP and lipid headgroups. Our LC-based methodology offers a potent and sensitive tool to detect and delineate molecular mechanisms of PrP misfolding mediated by lipid-protein interactions at the aqueous interface under physiological conditions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/acs.jpclett.3c02770 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Preanalytical Considerations of Handling Suspected Creutzfeldt-Jakob Disease Specimens Within the Clinical Pathology Laboratories: A Survey-Based Approach.
J Clin Med
January 2025
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA.
Creutzfeldt-Jakob disease (CJD) is a rare, fatal, and transmissible neurodegenerative disorder caused by prion proteins. Handling specimens from individuals with suspected or confirmed cases presents a safety challenge to hospital workers including clinical laboratory staff. As no national guidelines exist, the clinical pathology laboratory must establish protocols for handling these specimens to ensure sufficient protective measures.
View Article and Find Full Text PDFThe α-Synuclein Seeding Amplification Assay for Parkinson's Disease.
Int J Mol Sci
January 2025
National Neuroscience Institute of Singapore, 11 Jalan Tan Tock Seng, Singapore 30843, Singapore.
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Currently, PD is incurable, and the diagnosis of PD mainly relies on clinical manifestations. The central pathological event in PD is the abnormal aggregation and deposition of misfolded α-synuclein (α-Syn) protein aggregates in the Lewy body (LB) in affected brain areas.
View Article and Find Full Text PDFActivation and memory of the heatshock response is mediated by Prion-like domains of sensory HSFs in Arabidopsis.
Mol Plant
January 2025
Leibniz Institut für Gemüse und Zierpflanzenbau (IGZ) e.V., Großbeeren, Germany; Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany. Electronic address:
Plants are able to sense and remember heat stress. An initial priming heat stress enables plants to acclimate so that they are able to survive a subsequent higher temperature. The heatshock transcription factors (HSFs) play a crucial role in this process, but the mechanisms by which plants sense heat stress are not well understood.
View Article and Find Full Text PDFThe novel T107I Inherited prion disease can present as a clinical and biomarker mimic of familial Alzheimer's disease.
J Neurogenet
January 2025
Institute of Prion Diseases, MRC Prion Unit at University College London, London, UK.
Inherited prion diseases (IPD) secondary to mutations of the prion protein gene, exhibit diverse clinical phenotypes, capable of mimicking numerous primary neurodegenerative conditions. We describe the clinical phenotype and neuropathological findings in a family from County Limerick in Ireland presenting with Alzheimer's disease-like cognitive decline and motor symptoms caused by a novel missense mutation of This mutation occurs in the central lysine cluster (CLC; codon 101-110), resulting in substitution of threonine with isoleucine at codon 107 (T107I). This case series highlights that IPD can be hard to distinguish from overlapping clinical syndromes seen in other neurodegenerative diseases.
View Article and Find Full Text PDFChlorophyllides repress gain-of-function p53 mutated HNSCC cell proliferation via activation of p73 and repression of p53 aggregation in vitro and in vivo.
Biochim Biophys Acta Mol Basis Dis
January 2025
Department of Medical Science and Biotechnology, I-Shou University, Kaohsiung City 82445, Taiwan. Electronic address:
Head and neck squamous cell carcinoma (HNSCC) cells have a high p53 mutation rate, but there were rare reported about the p53 gain of function through the prion-like aggregated form in p53 mutated HNSCC cells. Thioflavin T (ThT) is used to stain prion-like proteins in cells. Previously, we found that ThT and p53 staining were co-localized in HNSCC cells (Detroit 562 cells) with homozygous p53 R175H mutation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!