Pharmacological PINK1 activation ameliorates Pathology in Parkinson’s Disease models DOI Open Access
R Chin,

Rishi Rakhit,

Dara Ditsworth

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 15, 2023

PINK1 loss-of-function mutations and exposure to mitochondrial toxins are causative for Parkinson's disease (PD) Parkinsonism, respectively. We demonstrate that pathological α-synuclein deposition, the hallmark pathology of idiopathic PD, induces dysfunction impairs mitophagy, driving accumulation substrate pS65-Ubiquitin (pUb) in primary neurons vivo. synthesized MTK458, a brain penetrant small molecule binds stabilizes an active heterocomplex, thereby increasing mitophagy. MTK458 mediates clearance PFF seeding models vitro vivo reduces pUb. developed ultrasensitive assay quantify pUb levels plasma observed increase PD subjects correlates with progression, paralleling our observations models. Our combined findings from preclinical patient biofluids suggest pharmacological activation is worthy further study as therapeutic strategy modification PD.Discovery Disease biomarker candidate, (pUb)Plasma correlate status progression patients.Identification potent, activator, MTK458MTK458 selectively activates by stimulating dimerization stabilization PINK1/TOM complexMTK458 drives normalizes

Language: Английский

Single Molecule Protein Detection with Attomolar Sensitivity Using Droplet Digital Enzyme-Linked Immunosorbent Assay DOI
Limor Cohen, Naiwen Cui,

Yamei Cai

et al.

ACS Nano, Journal Year: 2020, Volume and Issue: 14(8), P. 9491 - 9501

Published: June 26, 2020

Many proteins are present at low concentrations in biological samples, and therefore, techniques for ultrasensitive protein detection necessary. To overcome challenges with sensitivity, the digital enzyme-linked immunosorbent assay (ELISA) was developed, which is 1000× more sensitive than conventional ELISA allows sub-femtomolar detection. However, this sensitivity still not sufficient to measure many various thereby limiting our ability detect discover biomarkers. limitation, we developed droplet (ddELISA), a simple approach detecting levels using microfluidics. ddELISA achieves maximal by improving sampling efficiency counting target molecules. can attomolar range up 25-fold Single Molecule Arrays (Simoa), current gold standard tool Using ddELISA, measured LINE1/ORF1 protein, potential cancer biomarker that has been previously serum. Additionally, due simplicity of device design, promising point-of-care applications. Thus, will facilitate discovery biomarkers have never before clinical

Language: Английский

Citations

198
Single-cell analysis targeting the proteome DOI
Mahmoud Labib, Shana O. Kelley

Nature Reviews Chemistry, Journal Year: 2020, Volume and Issue: 4(3), P. 143 - 158

Published: Feb. 17, 2020

Language: Английский

Citations

196
Strategies to improve performances of LSPR biosensing: Structure, materials, and interface modification DOI

Tianping Xu,

Zhaoxin Geng

Biosensors and Bioelectronics, Journal Year: 2020, Volume and Issue: 174, P. 112850 - 112850

Published: Nov. 25, 2020

Language: Английский

Citations

160
Ultrabright fluorescent nanoscale labels for the femtomolar detection of analytes with standard bioassays DOI
Jingyi Luan, Anushree Seth, Rohit Gupta

et al.

Nature Biomedical Engineering, Journal Year: 2020, Volume and Issue: 4(5), P. 518 - 530

Published: April 20, 2020

Language: Английский

Citations

152
Emerging ELISA derived technologies for in vitro diagnostics DOI
Ping Peng, Chang Liu, Zedong Li

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2022, Volume and Issue: 152, P. 116605 - 116605

Published: March 25, 2022

Language: Английский

Citations

133
Framework for rapid comparison of extracellular vesicle isolation methods DOI Creative Commons
Dmitry Ter‐Ovanesyan, Maia Norman, Roey Lazarovits

et al.

eLife, Journal Year: 2021, Volume and Issue: 10

Published: Nov. 16, 2021

Extracellular vesicles (EVs) are released by all cells into biofluids and hold great promise as reservoirs of disease biomarkers. One the main challenges in studying EVs is a lack methods to quantify that sensitive enough can differentiate from similarly sized lipoproteins protein aggregates. We demonstrate use ultrasensitive, single-molecule array (Simoa) assays for quantification using three widely expressed transmembrane proteins: tetraspanins CD9, CD63, CD81. Using Simoa measure these EV markers, well albumin contamination, we were able compare relative efficiency purity several commonly used isolation plasma cerebrospinal fluid (CSF): ultracentrifugation, precipitation, size exclusion chromatography (SEC). further assays, on one platform, improve SEC CSF. Our results highlight utility quantifying proteins provide rapid framework comparing improving biofluids.

Language: Английский

Citations

109
High-Throughput, High-Multiplex Digital Protein Detection with Attomolar Sensitivity DOI

Connie Wu,

Tyler Dougan, David R. Walt

et al.

ACS Nano, Journal Year: 2022, Volume and Issue: 16(1), P. 1025 - 1035

Published: Jan. 14, 2022

A major challenge in many clinical diagnostic applications is the measurement of low-abundance proteins and other biomolecules biological fluids. Digital technologies such as digital enzyme-linked immunosorbent assay (ELISA) have enabled 1000-fold increases sensitivity over conventional protein detection methods. However, current ELISA still possess insufficient sensitivities for rare biomarkers require specialized instrumentation or time-consuming workflows that limited their widespread implementation. To address these challenges, we developed a more sensitive streamlined platform, Molecular On-bead Signal Amplification Individual Counting (MOSAIC), which attains low attomolar limits detection, with an order magnitude enhancement MOSAIC uses rapid, automatable flow cytometric readout vastly throughput easily integrated into existing laboratory infrastructure. As provides high sampling efficiencies target molecules, bead number can readily be tuned to enhance signal-to-background precision. Furthermore, solution-based signal expands analytes simultaneously measured higher-order multiplexing femtomolar below, compared microwell- droplet-based proof principle, apply toward improving detectability cytokines saliva ultrasensitive multiplexed measurements eight plasma saliva. The sensitivity, throughput, broad abilities provide highly accessible versatile capabilities potentially accelerate biomarker discovery testing diverse disease applications.

Language: Английский

Citations

94
Metal-Nanoparticle-Supported Nanozyme-Based Colorimetric Sensor Array for Precise Identification of Proteins and Oral Bacteria DOI

Zhanglu Lu,

Na Lü, Yang Xiao

et al.

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(9), P. 11156 - 11166

Published: Feb. 25, 2022

Convenient, precise, and high-throughput discrimination of multiple bioanalytes is great significance for an early diagnosis diseases. Array-based pattern recognition has proven to be a powerful tool detect diverse analytes, but developing sensing elements featuring favorable surface diversity still remains challenge. In this work, we presented simple facile method prepare programmable metal-nanoparticle (NP)-supported nanozymes (MNNs) as artificial receptors the accurate identification proteins oral bacteria. The in situ reduction metal NPs on hierarchical MoS2 polypyrrole (PPy), which generated differential nonspecific interactions with bioanalytes, was envisaged encoder break through limited supply receptor's quantity. As proof concept, three NPs, i.e., Au, Ag, Pd were taken examples deposit PPy@MoS2 colorimetric probes construct cross-reactive sensor array. Based principal component analysis (PCA), proposed MNN array could well discriminate 11 unique fingerprint-like patterns at concentration 250 nM sufficiently sensitive determine individual detection limit down nanomolar level. Remarkably, two highly similar hemoglobins from different species (hemoglobin bovine hemoglobin) have been precisely identified. Additionally, five bacteria also separated each other without cross-classification level 107 CFU mL-1. Furthermore, allowed effective complex protein mixtures either molar ratios or minor varying components. Most importantly, blind samples, human serums, simulated body fluid environment, heat-denatured proteins, even clinical cancer samples all distinguished by array, demonstrating real-world applications diagnosis.

Language: Английский

Citations

78
Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application DOI Creative Commons
Mingyang Li, Lei Li, Jianyi Zheng

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 21, 2023

Abstract Renal cell carcinoma (RCC) is a major pathological type of kidney cancer and one the most common malignancies worldwide. The unremarkable symptoms early stages, proneness to postoperative metastasis or recurrence, low sensitivity radiotherapy chemotherapy pose challenge for diagnosis treatment RCC. Liquid biopsy an emerging test that measures patient biomarkers, including circulating tumor cells, cell-free DNA/cell-free DNA, RNA, exosomes, tumor-derived metabolites proteins. Owing its non-invasiveness, liquid enables continuous real-time collection information diagnosis, prognostic assessment, monitoring, response evaluation. Therefore, selection appropriate biomarkers crucial identifying high-risk patients, developing personalized therapeutic plans, practicing precision medicine. In recent years, owing rapid development iteration extraction analysis technologies, has emerged as cost, high efficiency, accuracy clinical detection method. Here, we comprehensively review components their applications over past 5 years. Additionally, discuss limitations predict future prospects.

Language: Английский

Citations

51
Highly Sensitive Digital and Analog Immunoassay Based on Submicron Magnetic Beads and Fluorescent Microspheres DOI
Feng Gong,

Xiaoyun Shan,

Kebing Yi

et al.

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

The detection of disease-related protein biomarkers plays a crucial role in the early diagnosis, treatment, and monitoring diseases. concentrations can vary significantly different diseases or stages same disease. However, most existing analytical methods cannot simultaneously meet requirements high sensitivity wide dynamic range. Herein, we developed digital analog immunoassay method based on submicron magnetic beads fluorescent microspheres. analysis achieves limit as low 46 fg/mL (1.8 fM) for IL-6, has range spanning from 0.2 pg/mL to 10 ng/mL. Furthermore, be used quickly roughly assess higher concentration proteins via visual detection, practical application potential this was verified by alpha-fetoprotein serum samples 12 healthy individuals hepatocellular carcinoma patients. established does not involve use enzymes costly instruments, which greatly simplifies experimental steps, shortens time, reduces cost. In view those advantages, proposed great prospects point-of-care applications.

Language: Английский

Citations

2