How Does ABPP Contribute to Research on Tumors and Neurological Disorders?
- Distinguishing functional proteins from inactive or precursor forms
- Applicability to complex biological samples, including tumor tissues, brain tissues, and cerebrospinal fluid
- Revealing dynamic activity profiles by comparing disease and normal states
- Screening and customization of ABP probes for diverse enzyme classes
- Compatibility with cell, tissue, CSF, and animal model samples
- High-resolution analysis using the Orbitrap Exploris 480 mass spectrometer
- Professional services in target identification, pathway enrichment, and visualization of activity profiles
As research on disease mechanisms increasingly advances toward cellular functions and molecular dynamics, the limitation of proteomics, capable of detecting expression but not activity, has become more evident. Particularly in complex disorders such as tumors and neurological diseases, alterations in protein functional states often provide more accurate insights into biological processes than changes in expression levels.
Activity-Based Protein Profiling (ABPP), a representative technique in functional proteomics, has been widely applied to identify disease-related active proteases, functional targets, and potential biomarkers, owing to its ability to capture only active proteins. This article highlights the unique value of ABPP in tumor and neurological disease research, offering new perspectives for target discovery and mechanistic elucidation.
Overview of ABPP Technology
The principle of ABPP lies in the covalent labeling of enzymes in their active states using structurally specific probes, followed by identification and quantification through mass spectrometry (LC-MS/MS). Its key advantages include:
ABPP is particularly well-suited for investigating enzyme proteins (such as serine hydrolases, cysteine proteases, and deacetylases) in the context of activation, inactivation, and regulation under pathological conditions.
Application of ABPP in Tumor Research
A hallmark of tumor cells is the reprogramming of metabolic and signaling pathways. Many proteases involved in malignant transformation, invasion, and metastasis display aberrant activation in tumors, changes often undetectable by conventional proteomics.
1. Accurately Identifying Active Enzymatic Targets in Tumors
Certain matrix metalloproteinases (MMPs), although expressed at relatively low levels in the tumor microenvironment, exhibit abnormally elevated activity and contribute to basement membrane degradation and cancer cell migration. ABPP enables direct labeling of such enzymes, thereby mapping enzyme activity profiles within tumor tissues and pinpointing therapeutic targets with genuine potential.
2. Investigating Drug Mechanisms and Off-Target Effects
ABPP provides a powerful approach for characterizing the target spectra of small-molecule inhibitors. It can verify whether intended targets are inhibited while simultaneously detecting potential off-target protease activities, thereby mitigating adverse effects. For instance, during the development of protease inhibitors, ABPP is frequently used to validate compound specificity and assess unintended modulation of non-target proteins in vivo.
3. Development of Tumor Biomarkers
By comparing activity profiles between tumor tissues and adjacent normal tissues, ABPP may reveal tumor-specific enzymes activated exclusively in malignant tissues, offering potential biomarkers for liquid biopsy or early diagnosis.
Application of ABPP in Neurological Disease Research
Neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), are characterized by protein aggregation, dysregulated enzyme activity, and neuronal death. ABPP enables the identification of critical nodes of enzymatic dysregulation at early stages, thereby providing mechanistic insights and informing therapeutic strategies.
1. Elucidating Enzyme Activity Changes During Neurodegeneration
ABPP can monitor activity dynamics of cysteine proteases, such as caspases, across disease stages, helping to elucidate which enzymes are central to the initiation of neuronal apoptosis.
2. Functional Proteomic Comparison of Normal and Pathological Brain Tissues
Unlike conventional proteomics that focuses on expression levels, ABPP provides dynamic profiles of active proteases within neural tissues, facilitating:
(1) Preclinical evaluation during drug screening
(2) Identification of region-specific functional targets
(3) Mechanistic studies of neuroinflammatory processes
3. Advancing Cerebrospinal Fluid (CSF) Biomarker Development
Although CSF samples hold high clinical potential, their complexity and broad range of protein abundances present analytical challenges. ABPP enrichment significantly enhances the detection sensitivity of low-abundance active proteins, thereby supporting the development of early diagnostic biomarkers.
MtoZ Biolabs: Comprehensive ABPP Services for Tumor and Neurological Disease Research
To address the growing demand for ABPP in biomedical research, MtoZ Biolabs has established a complete service platform encompassing experimental design, probe labeling, enrichment, mass spectrometry, and data analysis. The platform includes:
The principal advantage of ABPP lies in its ability to determine not only protein expression but also whether proteins are functionally active. For highly complex diseases such as tumors and neurological disorders, activity-based information is essential for uncovering the fundamental disease mechanisms. MtoZ Biolabs offers high-sensitivity ABPP analyses of tumor and neurological samples, supporting applications in basic research, drug discovery, and target validation.
For investigators undertaking target screening, mechanistic studies, or pharmacological validation in tumor or neurological disease research, MtoZ Biolabs offers ABPP solutions characterized by broad coverage, high specificity, and robust visualization, thereby providing comprehensive support for research advancement.
MtoZ Biolabs, an integrated chromatography and mass spectrometry (MS) services provider.
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