ALS2CR11 Antibody

What is ALS2CR11 and what is its significance in neurodegenerative disease research?

ALS2CR11 (Amyotrophic Lateral Sclerosis 2 Chromosomal Region Candidate Gene 11) is a protein that has been identified in the chromosomal region associated with juvenile amyotrophic lateral sclerosis. This protein is also known as C2 calcium-dependent domain-containing protein 6 (C2CD6), reflecting its structural characteristics . The significance of ALS2CR11 lies in its potential role in the pathogenesis of neurodegenerative diseases, particularly ALS. While TDP-43 dysregulation has been established as a key pathological hallmark in ALS and frontotemporal dementia (FTD), the role of ALS2CR11 remains an area of active investigation. Research into proteins like ALS2CR11 may contribute to understanding disease mechanisms and potentially identifying novel biomarkers or therapeutic targets. Its investigation parallels other research efforts to find fluid biomarkers for presymptomatic or prodromal phases of ALS-FTD, which would enable earlier diagnosis and facilitate patient recruitment for clinical trials .

What are the known synonyms and alternative designations for ALS2CR11?

ALS2CR11 is known by several alternative names in the scientific literature and research databases. The primary synonyms include:

• C2 calcium-dependent domain-containing protein 6 (C2CD6)

• Cation channel sperm-associated targeting subunit tau (CatSper-tau)

• CATSPERT

In protein databases such as UniProt, ALS2CR11 is identified by:

• Primary accession number: Q53TS8

• Secondary accession numbers: C9IZH7, E9PGG4, Q8NCN6, Q96LN4

• Entry name: C2CD6_HUMAN

Additional database identifiers include:

• KEGG: hsa:151254

• String: 9606.ENSP00000409937

Understanding these alternative designations is essential when conducting literature searches or database queries to ensure comprehensive coverage of all relevant research.

What is the molecular weight and basic structural characterization of ALS2CR11?

ALS2CR11 has a molecular weight of approximately 71 kDa, which is important to know when validating antibody specificity in Western blot applications . The protein contains C2 calcium-dependent domains, as indicated by its alternative name (C2CD6). These domains are typically involved in calcium-dependent membrane targeting. The full protein structure has not been comprehensively characterized in the available search results, but researchers studying this protein should be aware that it likely functions in calcium-dependent cellular processes.

When designing experiments to study ALS2CR11, researchers should consider these structural features, particularly when selecting antibodies. For example, the antibody described in search result targets a synthetic peptide derived from human ALS2CR11 (amino acids 491-540), suggesting this region may contain important epitopes for antibody recognition. Similarly, the antibody in search result is raised against the C-terminal region of the protein. Understanding these structural aspects helps in experimental design, particularly for protein interaction studies, localization experiments, or functional assays that might be affected by the calcium-dependent domains.

What are the optimal applications for different types of ALS2CR11 antibodies?

Based on the available research data, ALS2CR11 antibodies have been validated for several experimental applications with varying performance characteristics. The selection of the appropriate antibody depends on the specific research question and experimental design.

For Western blot applications, all listed antibodies have been validated, making this the most robust application across available antibodies. For immunocytochemistry (ICC) and immunofluorescence (IF), ABIN6258698 appears to be the most versatile option, while ABIN654732 is unique in being validated for flow cytometry (FACS) applications .

When designing experiments, consider the specific epitope targeted by each antibody. For instance, the Abbexa antibody targets the C-terminal region of human ALS2CR11 , while antibody A99973 specifically recognizes amino acids 491-540 . This epitope information is crucial for applications where protein conformation or post-translational modifications might affect antibody binding.

What are the best practices for Western blot protocol optimization using ALS2CR11 antibodies?

When optimizing Western blot protocols for ALS2CR11 detection, researchers should consider several technical aspects:

• Sample Preparation: ALS2CR11 has a molecular weight of 71 kDa , so standard protein extraction methods should be suitable. Use protease inhibitors in your lysis buffer to prevent degradation.

• Antibody Selection and Dilution:

  • For the Abbexa antibody, use a dilution range of 1/500 - 1/3000

  • For antibody A99973, use a dilution range of 1:500-1:1000

  • Begin with the manufacturer's recommended dilution and adjust based on signal strength and background

• Blocking Conditions: Given that these are polyclonal antibodies, 5% non-fat milk or 3-5% BSA in TBST is typically sufficient for blocking non-specific binding sites.

• Validation Controls: Include both positive controls (cell lines known to express ALS2CR11) and negative controls (either knockdown samples or non-expressing tissues) to confirm specificity.

• Secondary Antibody Selection: For the rabbit polyclonal antibodies (Abbexa and A99973), recommended secondary antibodies include:

  • Goat Anti-Rabbit IgG H&L Antibody (AP) (A294874)

  • Goat Anti-Rabbit IgG H&L Antibody (Biotin) (A294795)

  • Goat Anti-Rabbit IgG H&L Antibody (FITC) (A294887)

  • Goat Anti-Rabbit IgG H&L Antibody (HRP) (A294888)

• Detection Method: HRP-conjugated secondary antibodies with ECL substrate are commonly used, but for low expression levels, more sensitive detection methods may be required.

• Troubleshooting: If experiencing high background, increase the number or duration of wash steps or further dilute the primary antibody. If signal is weak, consider longer exposure times, increased antibody concentration, or signal enhancement systems.

The Western blot validation image available for antibody A99973 demonstrates successful detection of ALS2CR11, providing evidence for the effectiveness of these protocols when properly optimized.

How should researchers approach ELISA protocol development for ALS2CR11 detection?

For developing ELISA protocols to detect ALS2CR11, researchers should consider the following methodological approaches:

• Antibody Selection: Multiple antibodies are validated for ELISA applications, including ABIN6258698, ABIN3183257, the Abbexa antibody, and A99973 . Different antibodies may have different sensitivities and specificities.

• Antibody Dilutions:

  • The Abbexa antibody recommends a dilution of 1/40000 for ELISA applications

  • Antibody A99973 recommends a dilution of 1:10000

  • These highly diluted concentrations suggest good sensitivity in ELISA format

• Plate Coating: For direct ELISA, coat plates with your sample. For sandwich ELISA, use one ALS2CR11 antibody as capture antibody and another (preferably recognizing a different epitope) as detection antibody.

• Standard Curve Development: If quantifying ALS2CR11, consider using recombinant ALS2CR11 protein (such as ABIN1344951 ) as a standard to generate a calibration curve.

• Sample Types: The available antibodies have been validated with human samples , with ABIN6258698 also showing reactivity with mouse samples . Consider species cross-reactivity when designing experiments.

• Controls: Include both positive controls (samples known to contain ALS2CR11) and negative controls (buffer only or samples known not to contain ALS2CR11).

• Detection System: For unconjugated primary antibodies, use an appropriate enzyme-conjugated secondary antibody system matched to your primary antibody host species.

• Validation: Confirm ELISA results with another method such as Western blot to ensure specificity, particularly in complex biological samples.

For researchers studying ALS2CR11 in the context of neurodegenerative diseases, developing a sensitive ELISA could potentially contribute to biomarker discovery efforts similar to those being pursued for TDP-43-related biomarkers in ALS-FTD .

How can ALS2CR11 antibodies be utilized in studying its potential role in ALS pathogenesis?

To investigate ALS2CR11's potential role in ALS pathogenesis, researchers can employ several advanced experimental approaches utilizing available antibodies:

• Tissue Expression Profiling: Use immunohistochemistry with ALS2CR11 antibodies (like ABIN6258698, which is validated for ICC/IF ) to compare expression patterns in postmortem tissues from ALS patients versus controls. Focus on motor neurons, the primary affected cell type in ALS.

• Protein-Protein Interaction Studies: Employ ALS2CR11 antibodies for co-immunoprecipitation experiments to identify interaction partners, particularly with known ALS-associated proteins like TDP-43, which is known to be dysregulated in ALS .

• Subcellular Localization Studies: Use immunofluorescence with ALS2CR11 antibodies to determine if the protein's subcellular localization changes in disease states, similar to the nuclear-to-cytoplasmic mislocalization observed with TDP-43 in ALS .

• Animal Model Validation: ABIN6258698 shows cross-reactivity with mouse samples , enabling studies in ALS mouse models to correlate ALS2CR11 expression or localization with disease progression.

• Patient-Derived Cell Models: Apply ALS2CR11 antibodies in immunofluorescence or Western blot studies of iPSC-derived motor neurons from ALS patients versus controls to investigate expression changes.

• Biomarker Investigation: Given recent advances in identifying fluid biomarkers for ALS , researchers could explore whether ALS2CR11 levels in cerebrospinal fluid or blood correlate with disease progression, using techniques like ELISA with the validated antibodies.

• Functional Studies: Combine ALS2CR11 antibodies with calcium imaging techniques to investigate whether the calcium-dependent domains of ALS2CR11 (C2CD6) play a role in calcium dysregulation, which has been implicated in ALS pathogenesis.

These approaches would enable researchers to build a comprehensive understanding of ALS2CR11's potential contribution to ALS, placing it in context with established disease mechanisms like TDP-43 pathology.

What considerations should researchers take into account when investigating potential interactions between ALS2CR11 and other ALS-associated proteins?

When investigating interactions between ALS2CR11 and other ALS-associated proteins, researchers should consider several methodological and biological factors:

• Selection of Interaction Partners: Prioritize proteins with established roles in ALS pathogenesis, such as:

  • TDP-43, which shows nuclear mislocalization and loss of splicing repression in ALS

  • SOD1, which forms aggregates in some familial ALS cases

  • FUS, another RNA-binding protein implicated in ALS

  • C9orf72, associated with the most common genetic form of ALS

• Co-immunoprecipitation Approach:

  • Use ALS2CR11 antibodies (like the Abbexa antibody or A99973 ) as "bait" to pull down potential interacting proteins

  • Perform reverse co-IP using antibodies against candidate interacting proteins

  • Validate interactions using multiple antibodies targeting different epitopes to confirm specificity

• Proximity Ligation Assays:

  • Combine ALS2CR11 antibodies with antibodies against potential interacting partners

  • This technique can visualize protein interactions in situ within cells or tissues with high specificity

• Functional Relevance:

  • Consider the C2 calcium-dependent domains of ALS2CR11 (C2CD6) and how they might mediate interactions

  • Investigate if interactions are calcium-dependent by performing experiments in varying calcium concentrations

• Disease Context:

  • Compare interaction patterns in normal versus disease states (using ALS patient samples or models)

  • Determine if interactions are altered in response to cellular stressors relevant to ALS

• Technical Considerations:

  • Ensure antibodies used recognize native protein conformations if studying interactions in non-denaturing conditions

  • Consider epitope availability in protein complexes; antibodies targeting regions involved in protein-protein interactions may show reduced binding

• Controls and Validation:

  • Include isotype controls (like Rabbit IgG A82272 or A17360 ) in co-IP experiments

  • Validate key findings using alternative methods (e.g., proximity ligation, FRET, yeast two-hybrid)

Understanding these potential interactions could provide insights into whether ALS2CR11 participates in established ALS pathogenic pathways or represents a novel disease mechanism.

How can researchers integrate ALS2CR11 studies with emerging biomarker research in neurodegenerative diseases?

Integrating ALS2CR11 studies with emerging biomarker research in neurodegenerative diseases requires a strategic approach that connects fundamental protein biology with clinical applications:

• Correlation with Established Biomarkers: Compare ALS2CR11 expression or modifications with emerging biomarkers like the TDP-43-dependent cryptic epitope in HDGFL2, which has shown promise as an early biomarker for ALS-FTD, even in presymptomatic stages . This comparison could establish whether ALS2CR11 changes precede, coincide with, or follow other biomarker changes.

• Fluid Biomarker Development:

  • Adapt existing ELISA protocols using validated ALS2CR11 antibodies to detect the protein in cerebrospinal fluid (CSF) and blood samples

  • Compare levels between ALS patients, those with other neurodegenerative diseases, and healthy controls

  • Investigate whether levels correlate with disease progression, similar to analyses performed with neurofilament light and phosphorylated neurofilament heavy chain proteins

• Longitudinal Studies:

  • Monitor ALS2CR11 levels in biological fluids from presymptomatic mutation carriers (e.g., C9orf72 mutation carriers) through disease progression

  • Determine if changes in ALS2CR11 could serve as early diagnostic markers or predictors of disease onset

• Multiplex Biomarker Panels:

  • Develop assays that simultaneously measure ALS2CR11 alongside other promising biomarkers

  • Assess whether combinations of biomarkers provide better diagnostic or prognostic value than single markers

• Target Engagement Markers:

  • Evaluate whether ALS2CR11 levels or modifications could serve as pharmacodynamic markers in clinical trials, similar to how researchers are exploring TDP-43-related markers

• Methodology Standardization:

  • Establish standardized protocols for ALS2CR11 detection in clinical samples

  • Conduct inter-laboratory validation to ensure reproducibility of results

• Cross-Disease Comparisons:

  • Investigate ALS2CR11 as a potential biomarker across the ALS-FTD spectrum and related neurodegenerative conditions

  • Determine if it shows disease specificity or represents a more general marker of neurodegeneration

By integrating ALS2CR11 studies with broader biomarker research, researchers can potentially contribute to improving early diagnosis, patient stratification for clinical trials, and monitoring of disease progression and treatment response in ALS and related neurodegenerative diseases.

What are common challenges in ALS2CR11 antibody experiments and how can researchers overcome them?

Researchers working with ALS2CR11 antibodies may encounter several technical challenges. Here are common issues and strategies to address them:

• Low Signal Intensity in Western Blots:

  • Problem: Weak or absent bands despite proper sample preparation.

  • Solutions:

    • Optimize antibody concentration (try the more concentrated end of recommended dilutions, e.g., 1/500 for Abbexa antibody or 1:500 for A99973 )

    • Increase protein loading (30-50 μg total protein)

    • Extend primary antibody incubation (overnight at 4°C)

    • Use enhanced chemiluminescence substrates designed for higher sensitivity

    • Consider membrane transfer optimization (extend transfer time for high molecular weight proteins)

• Non-specific Binding and High Background:

  • Problem: Multiple bands or high background obscuring specific signal.

  • Solutions:

    • Increase blocking time or concentration (e.g., 5% milk/BSA for 2 hours)

    • More stringent washing (increase number of washes and duration)

    • Further dilute primary antibody

    • Add 0.1-0.5% Tween-20 to antibody dilution buffer

    • Use more specific secondary antibodies and consider cross-adsorbed versions

• Cross-Reactivity Issues:

  • Problem: Signal in samples where ALS2CR11 should not be present.

  • Solutions:

    • Validate with positive and negative controls

    • Perform knockdown/knockout validation

    • Try alternative antibodies that target different epitopes

    • Pre-absorb antibody with recombinant ALS2CR11 protein as a competition control

• Inconsistent ELISA Results:

  • Problem: High variability between replicates or experiments.

  • Solutions:

    • Standardize sample preparation methods

    • Carefully control incubation times and temperatures

    • Use automated plate washers if available

    • Develop a robust standard curve using recombinant ALS2CR11 protein

    • Consider sandwich ELISA approach using two different antibodies

• Poor Immunostaining Results:

  • Problem: Weak or non-specific staining in ICC/IF applications.

  • Solutions:

    • Optimize fixation method (try both paraformaldehyde and methanol fixation)

    • Test different antigen retrieval methods

    • Increase antibody concentration (for ABIN6258698 , which is validated for ICC/IF)

    • Extend primary antibody incubation time

    • Use signal amplification systems

• Storage and Stability Issues:

  • Problem: Decreased antibody performance over time.

  • Solutions:

    • Store antibodies according to manufacturer recommendations (typically aliquoted at -20°C)

    • Avoid repeated freeze-thaw cycles

    • Add carrier protein (BSA) to diluted antibody solutions

    • Check for visible precipitation before use

By systematically addressing these challenges, researchers can optimize their experimental protocols for studying ALS2CR11 in neurodegenerative disease research.

How should researchers interpret unexpected molecular weight variations of ALS2CR11 in Western blot results?

When researchers encounter unexpected molecular weight variations of ALS2CR11 in Western blot results, systematic analysis is required to determine whether these represent biologically significant variants or technical artifacts:

• Expected vs. Observed Molecular Weight:

  • The expected molecular weight of ALS2CR11 is approximately 71 kDa

  • Variations may represent:

    • Post-translational modifications

    • Alternative splicing variants

    • Proteolytic processing

    • Technical artifacts

• Assessment of Higher Molecular Weight Bands:

  • Potential biological explanations:

    • Ubiquitination or SUMOylation (typically adding 8-20 kDa increments)

    • Glycosylation (variable size increases)

    • Protein dimerization or complex formation (if sample preparation includes incomplete denaturation)

  • Validation approaches:

    • Treat samples with deglycosylation enzymes to determine if glycosylation contributes to size shifts

    • Use stronger reducing conditions to disrupt potential dimers

    • Perform immunoprecipitation followed by mass spectrometry to identify modifications

• Assessment of Lower Molecular Weight Bands:

  • Potential biological explanations:

    • Alternative splicing variants (check genomic databases for predicted variants)

    • Proteolytic cleavage products (potentially disease-relevant)

    • C-terminal or N-terminal truncations

  • Validation approaches:

    • Compare results using antibodies targeting different epitopes (N-terminal vs C-terminal)

    • Include protease inhibitors in sample preparation to determine if bands represent degradation products

    • Perform RT-PCR to detect alternative transcripts

• Technical Considerations:

  • Sample preparation artifacts:

    • Insufficient denaturation (leading to aberrant migration)

    • Protein degradation during extraction

    • Incomplete transfer of high molecular weight proteins

  • Gel percentage effects:

    • Lower percentage gels (6-8%) provide better resolution for higher molecular weight variants

    • Higher percentage gels (12-15%) better resolve smaller fragments

• Tissue or Cell-Type Specific Variations:

  • Compare patterns across different tissues or cell types

  • Determine if variations correlate with disease state or experimental conditions

  • Consider whether variations are consistent across biological replicates

• Confirmation Strategies:

  • Peptide competition assays to confirm specificity of variant bands

  • siRNA knockdown to determine which bands decrease with reduced expression

  • Overexpression of ALS2CR11 to identify which bands increase

  • Mass spectrometry of excised bands for definitive identification

Understanding these variations could potentially reveal disease-relevant modifications of ALS2CR11, particularly in the context of neurodegenerative conditions where protein modifications often play important pathogenic roles.

What statistical approaches are recommended for quantitative analysis of ALS2CR11 expression in comparative studies?

• Sample Size Determination:

  • Perform power analysis before beginning experiments to determine appropriate sample size

  • For human studies in neurodegenerative diseases, consider the inherent variability and aim for larger sample sizes when feasible

  • For cell culture experiments, ensure at least 3-5 biological replicates and multiple technical replicates

• Normalization Strategies for Western Blot Analysis:

  • Normalize ALS2CR11 signal to appropriate loading controls:

    • Housekeeping proteins (β-actin, GAPDH, tubulin) for total protein normalization

    • Compartment-specific markers if studying subcellular fractions

  • Consider total protein normalization methods (Ponceau S, REVERT, Stain-Free technology) to avoid issues with variable housekeeping protein expression

• Densitometry Quantification:

  • Use linear range of detection for quantification

  • Avoid saturated signals which prevent accurate quantification

  • Analyze band intensity using software like ImageJ, Image Lab, or similar programs

  • Apply background subtraction consistently across all samples

• Statistical Tests for Two-Group Comparisons:

  • For normally distributed data: Independent t-test with Welch's correction if variances differ

  • For non-normally distributed data: Mann-Whitney U test

  • Report both p-values and effect sizes (Cohen's d or similar)

• Statistical Tests for Multi-Group Comparisons:

  • For normally distributed data: One-way ANOVA with appropriate post-hoc tests (Tukey, Bonferroni, or Dunnett's depending on comparison needs)

  • For non-normally distributed data: Kruskal-Wallis with Dunn's post-hoc test

  • Control for multiple comparisons to reduce Type I error

• ELISA Data Analysis:

  • Generate standard curves using appropriate regression models (4-parameter logistic for most ELISAs)

  • Report intra-assay and inter-assay coefficients of variation

  • Calculate sample concentrations from the linear portion of the standard curve

  • Confirm that samples fall within the assay's quantifiable range

• Correlation Analysis:

  • When comparing ALS2CR11 levels with clinical parameters or other biomarkers:

    • Pearson correlation for normally distributed data

    • Spearman correlation for non-normally distributed data

  • Consider multiple regression models to account for confounding variables

• Longitudinal Data Analysis:

  • For studies tracking ALS2CR11 levels over time:

    • Repeated measures ANOVA or mixed-effects models

    • Survival analysis methods if correlating with disease progression

• Reporting Standards:

  • Include all data points in graphical representations when possible

  • Report measures of central tendency AND dispersion (mean±SD or median with interquartile range)

  • Clearly state statistical tests used and significance thresholds

  • Consider graphical representation of effect sizes alongside p-values

These statistical approaches will help ensure robust, reproducible quantitative analysis of ALS2CR11 expression in comparative studies, particularly important in the context of biomarker research for neurodegenerative diseases.

What emerging technologies could enhance ALS2CR11 detection and functional characterization?

Several cutting-edge technologies hold promise for advancing ALS2CR11 detection and functional characterization in neurodegenerative disease research:

• Advanced Imaging Technologies:

  • Super-resolution microscopy (STORM, PALM, STED) could reveal precise subcellular localization of ALS2CR11 beyond the capabilities of conventional microscopy, using existing antibodies validated for immunofluorescence like ABIN6258698

  • Expansion microscopy could physically enlarge specimens to visualize ALS2CR11 distribution within cellular compartments

  • Lattice light-sheet microscopy would allow long-term live-cell imaging to track ALS2CR11 dynamics with minimal phototoxicity

• Single-Cell Analysis Methods:

  • Single-cell proteomics could detect cell-to-cell variations in ALS2CR11 expression that might be masked in bulk tissue analysis

  • Mass cytometry (CyTOF) with metal-conjugated ALS2CR11 antibodies would allow simultaneous detection of multiple proteins in single cells

  • Spatial transcriptomics combined with immunodetection could correlate ALS2CR11 protein localization with gene expression patterns

• Proximity-Based Protein Interaction Methods:

  • BioID or APEX proximity labeling using ALS2CR11 fusion constructs would identify neighboring proteins in living cells

  • Split-protein complementation assays could validate specific protein-protein interactions in cellular contexts

  • FRET/FLIM analyses using fluorescently-tagged ALS2CR11 could detect direct protein interactions and conformational changes

• Advanced Protein Modification Analysis:

  • Top-down proteomics approaches could characterize intact ALS2CR11 and its proteoforms

  • Targeted mass spectrometry (PRM/MRM) could quantify specific ALS2CR11 peptides or post-translational modifications with high sensitivity

  • Phospho-specific antibodies could be developed to track activity-dependent modifications of ALS2CR11

• CRISPR-Based Technologies:

  • CRISPR activation/inhibition (CRISPRa/CRISPRi) could modulate ALS2CR11 expression without altering the genomic sequence

  • CRISPR knock-in of fluorescent tags could enable live imaging of endogenous ALS2CR11

  • Base editing or prime editing could introduce specific mutations to study structure-function relationships

• Microfluidic and Organ-on-Chip Technologies:

  • Microfluidic-based protein analysis could enable ultra-sensitive detection of ALS2CR11 in limited samples

  • Neuromuscular junction-on-chip models could explore ALS2CR11 function in a physiologically relevant context for ALS research

  • Blood-brain barrier models could investigate if ALS2CR11 crosses from CNS to periphery, relevant for biomarker development

• Ultrasensitive Detection Methods:

  • Single-molecule array (Simoa) technology could detect ALS2CR11 at femtomolar concentrations in biological fluids

  • Surface plasmon resonance (SPR) or biolayer interferometry (BLI) could characterize antibody-antigen interactions with high precision

  • Digital ELISA approaches could improve sensitivity for detecting ALS2CR11 in CSF or blood samples

Integration of these emerging technologies with existing antibody resources would significantly advance our understanding of ALS2CR11's role in health and disease, potentially contributing to biomarker development for neurodegenerative diseases.

How might characterization of ALS2CR11 contribute to personalized medicine approaches in ALS?

The comprehensive characterization of ALS2CR11 could significantly impact personalized medicine approaches in ALS through several interconnected pathways:

• Biomarker-Based Patient Stratification:

  • ALS2CR11 detection using validated antibodies could potentially identify distinct patient subgroups with different disease mechanisms

  • Combined with other biomarkers like the HDGFL2 cryptic epitope , ALS2CR11 could help create biomarker signatures for different ALS subtypes

  • This stratification could enable:

    • More homogeneous patient groups for clinical trials

    • Targeted therapeutic approaches based on specific disease mechanisms

    • More accurate prognosis prediction at individual patient level

• Pharmacodynamic Monitoring:

  • Changes in ALS2CR11 levels or modifications could serve as indicators of target engagement in clinical trials

  • Similar to how researchers are using TDP-43-related biomarkers , ALS2CR11 measurements could help determine if therapeutic interventions are having desired molecular effects

  • This would allow:

    • Earlier assessment of treatment efficacy

    • Dose optimization for individual patients

    • Identification of treatment responders versus non-responders

• Presymptomatic Disease Detection:

  • If ALS2CR11 abnormalities occur early in disease pathogenesis, antibody-based detection methods could identify individuals at risk before symptom onset

  • This parallels findings with TDP-43-dependent cryptic epitopes in presymptomatic C9orf72 mutation carriers

  • Benefits include:

    • Window for preventive interventions

    • Earlier enrollment in clinical trials when therapeutic benefit may be maximized

    • Extended monitoring period to understand disease progression mechanisms

• Therapeutic Target Identification:

  • Detailed characterization of ALS2CR11 function and interactions could reveal:

    • Druggable pathways specific to certain patient populations

    • Opportunities for gene therapy approaches in cases with ALS2CR11 abnormalities

    • Potential for antibody-based therapeutics targeting specific ALS2CR11 conformations

• Integration with Genetic Information:

  • Correlating ALS2CR11 expression or modifications with genetic variants could:

    • Identify genotype-phenotype relationships

    • Reveal how specific mutations affect ALS2CR11 function

    • Guide genetic counseling and risk assessment

• Liquid Biopsy Development:

  • Optimized antibody-based detection methods for ALS2CR11 in blood or CSF could:

    • Enable non-invasive longitudinal monitoring

    • Facilitate repeated sampling to track disease progression

    • Support at-home monitoring technologies for personalized care

• Treatment Response Prediction:

  • Baseline ALS2CR11 measurements might predict which patients will respond to specific therapies

  • Changes in ALS2CR11 early after treatment initiation could indicate long-term response probability

  • This would allow treatment plan adjustments based on individual molecular responses

These personalized medicine applications would leverage the antibody resources identified in the search results and build upon emerging biomarker approaches in the ALS-FTD field , ultimately improving patient care through more individualized treatment strategies.

What are the key methodological considerations researchers should remember when working with ALS2CR11 antibodies?

When working with ALS2CR11 antibodies in neurodegenerative disease research, several critical methodological considerations should guide experimental design and execution:

• Antibody Selection and Validation:

  • Choose antibodies based on the specific research question and required applications (WB, ELISA, ICC/IF, FACS)

  • Verify antibody specificity through multiple validation methods (knockdown controls, recombinant protein, multiple antibodies targeting different epitopes)

  • Consider the specific epitope recognized by each antibody and how this might affect detection in different experimental contexts

• Species Considerations:

  • Most available ALS2CR11 antibodies are validated for human samples, with only ABIN6258698 confirmed for mouse reactivity

  • Carefully validate antibodies when working with other model organisms

  • Consider potential cross-species differences in ALS2CR11 sequence and structure

• Technical Protocol Optimization:

  • Follow manufacturer-recommended dilutions initially (WB: 1:500-1:3000; ELISA: 1:10000-1:40000)

  • Optimize protocol conditions including blocking reagents, incubation times, and washing steps

  • Standardize sample preparation methods for consistent results

• Controls and Reproducibility:

  • Include appropriate positive and negative controls in every experiment

  • Utilize isotype controls (like Rabbit IgG) for immunoprecipitation and other applications

  • Perform biological replicates to ensure reproducibility of findings

• Quantification and Statistical Analysis:

  • Use appropriate normalization methods when quantifying ALS2CR11 expression

  • Apply rigorous statistical approaches suited to the experimental design

  • Report both technical variability (assay performance) and biological variability (sample differences)

• Integration with Other Methodologies:

  • Combine antibody-based detection with complementary approaches (e.g., mRNA expression, proteomics)

  • Consider how antibody-based findings can be validated using genetic or pharmacological manipulation

  • Interpret antibody-based results in the context of functional studies

• Translational Considerations:

  • When developing biomarker applications, validate findings in well-characterized patient cohorts

  • Consider pre-analytical variables that might affect ALS2CR11 detection in clinical samples

  • Establish reference ranges and assess assay performance metrics (sensitivity, specificity, reproducibility)