2024-08-05 ミネソタ大学
<関連情報>
- https://cse.umn.edu/college/news/new-visual-technique-could-advance-early-detection-neurodegenerative-diseases
- https://www.nature.com/articles/s44328-024-00003-0
- https://pubs.acs.org/doi/10.1021/acs.nanolett.3c01001
キャピラリーベースのクエーキング誘導変換アッセイ(Cap-QuIC)によるミスフォールドしたαシヌクレインとプリオンの視覚的検出 Visual detection of misfolded alpha-synuclein and prions via capillary-based quaking-induced conversion assay (Cap-QuIC)
Peter R. Christenson,Hyeonjeong Jeong,Hyerim Ahn,Manci Li,Gage Rowden,Rachel L. Shoemaker,Peter A. Larsen,Hye Yoon Park & Sang-Hyun Oh
npj Biosensing Published:26 June 2024
DOI:https://doi.org/10.1038/s44328-024-00003-0
Abstract
Neurodegenerative protein misfolding diseases impact tens of millions of people worldwide, contributing to millions of deaths and economic hardships across multiple scales. The prevalence of neurodegenerative disease is predicted to greatly increase over the coming decades, yet effective diagnostics for such diseases are limited. Most diagnoses come from the observation of external symptoms in clinical settings, which typically manifest during relatively advanced stages of disease, thus limiting potential therapeutic applications. While progress is being made on biomarker testing, the underlying methods largely rely on fragile and expensive equipment that limits their point-of-care potential, especially in developing countries. Here we present Capillary-based Quaking Induced Conversion (Cap-QuIC) as a visual diagnostic assay based on simple capillary action for the detection of neurodegenerative disease without necessitating expensive and complex capital equipment. We demonstrate that Cap-QuIC has the potential to be a detection tool for a broad range of misfolded proteins by successfully distinguishing misfolded versus healthy proteins associated with Parkinson’s disease (α-synuclein) and Chronic Wasting Disease (prions). Additionally, we show that Cap-QuIC can accurately classify biological tissue samples from wild white-tailed deer infected with Chronic Wasting Disease. Our findings elucidate the underlying mechanism that enables the Cap-QuIC assay to distinguish misfolded protein, highlighting its potential as a diagnostic technology for neurodegenerative diseases.
ミスフォールドタンパク質のナノ粒子強化RT-QuIC(ナノQuIC)診断アッセイ Nanoparticle-Enhanced RT-QuIC (Nano-QuIC) Diagnostic Assay for Misfolded Proteins
Peter R. Christenson,Manci Li,Gage Rowden,Peter A. Larsen,Sang-Hyun Oh
Nano Letters Published: April 26, 2023
DOI:https://doi.org/10.1021/acs.nanolett.3c01001
Abstract
Misfolded proteins associated with various neurodegenerative diseases often accumulate in tissues or circulate in biological fluids years before the clinical onset, thus representing ideal diagnostic targets. Real-time quaking-induced conversion (RT-QuIC), a protein-based seeded-amplification assay, holds great potential for early disease detection, yet challenges remain for routine diagnostic application. Chronic Wasting Disease (CWD), associated with misfolded prion proteins of cervids, serves as an ideal model for evaluating new RT-QuIC methodologies. In this study, we investigate the previously untested hypothesis that incorporating nanoparticles into RT-QuIC assays can enhance their speed and sensitivity when applied to biological samples. We show that adding 50 nm silica nanoparticles to RT-QuIC experiments (termed Nano-QuIC) for CWD diagnostics greatly improves the performance by reducing detection times 2.5-fold and increasing sensitivity 10-fold by overcoming the effect of inhibitors in complex tissue samples. Crucially, no false positives were observed with these 50 nm silica nanoparticles, demonstrating the enhanced reliability and potential for diagnostic application of Nano-QuIC in detecting misfolded proteins.
