HMGB1 Antibody
Description
Structure and Function of HMGB1
HMGB1 is a 215-amino-acid protein containing:
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Two DNA-binding HMG boxes (A and B): Bind DNA and regulate gene expression.
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C-terminal acidic tail: Modulates chromatin structure.
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Nuclear localization signals (NLS1 and NLS2): Direct nuclear retention.
Post-translational modifications (e.g., acetylation, phosphorylation) dictate its subcellular localization and function . Extracellular HMGB1 acts as a damage-associated molecular pattern (DAMP), signaling through receptors like RAGE, TLR2, and TLR4 .
Types of HMGB1 Antibodies
HMGB1 antibodies are categorized by their origin and reactivity:
Key monoclonal antibodies like MAB16901 target the B-box for neutralizing proinflammatory activity , while polyclonal antibodies detect full-length HMGB1 in diverse assays .
Therapeutic Applications
HMGB1 antibodies show promise in treating diseases driven by excessive inflammation:
Central Nervous System (CNS) Disorders
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Ischemic Stroke: Anti-HMGB1 monoclonal antibodies (mAbs) reduce cerebral edema and neuroinflammation by suppressing IL-1β, TNF-α, and MMPs .
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Traumatic Brain Injury (TBI): Preclinical studies demonstrate improved cognitive recovery via HMGB1 neutralization .
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Neurodegenerative Diseases: HMGB1 mAbs mitigate Parkinson’s and Alzheimer’s disease progression by reducing microglial activation .
Autoimmune Diseases
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Systemic Lupus Erythematosus (SLE): Elevated anti-HMGB1 antibodies correlate with disease activity and renal involvement .
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Sjögren’s Syndrome (SS): HMGB1 antibodies are proposed as diagnostic markers (sensitivity: 64.5%, specificity: 96.9%) .
Diagnostic Utility
HMGB1 antibodies are used to detect and characterize autoimmune conditions:
Serum HMGB1 levels are higher in infectious/autoimmune subgroups compared to malignancies .
Mechanisms of Action
HMGB1 antibodies exert effects through:
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Neutralization: Binding to HMGB1 prevents interaction with RAGE/TLRs, inhibiting NF-κB-driven cytokine release .
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Modulation of Post-Translational Modifications:
Preclinical Efficacy
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Stroke Models: Anti-HMGB1 mAbs reduce IL-1β-positive microglia and vasoconstriction-related receptors (e.g., AT-1, PAR-1) in peri-hematomal regions .
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Arthritis: HMGB1 mAbs suppress TNF-α and IL-6 in murine polyarthritis .
Challenges
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Cross-Reactivity: Polyclonal antibodies may detect HMGB1 isoforms or post-translational variants .
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Therapeutic Delivery: Blood-brain barrier penetration limits CNS applications .
Future Directions
Product Specs
Product Science Overview
High-Mobility Group Box 1 (HMGB1) is a non-histone chromatin-associated protein that plays a crucial role in various cellular processes and disease mechanisms. It is a highly conserved protein found in the nucleus of eukaryotic cells and is involved in DNA binding, transcriptional regulation, and chromatin remodeling .
HMGB1 consists of 215 amino acids and has a molecular weight of approximately 30 kDa. It is composed of two DNA-binding domains (HMG boxes A and B) and an acidic C-terminal tail. The protein can bind to DNA and bend it, facilitating the assembly of nucleoprotein complexes .
Intracellularly, HMGB1 is involved in:
- Transcriptional regulation: It acts as a co-factor for various transcription factors.
- DNA repair: It participates in the recognition and repair of damaged DNA.
- Chromatin remodeling: It helps in the structural organization of chromatin.
Extracellularly, HMGB1 can be released into the extracellular space during cell stress, injury, or necrosis. In this context, it acts as a damage-associated molecular pattern (DAMP) molecule, triggering inflammatory responses by binding to pattern recognition receptors (PRRs) such as TLR4 and RAGE .
HMGB1 is implicated in various diseases, including:
- Cancer: It promotes tumor growth, metastasis, and resistance to chemotherapy.
- Inflammatory diseases: It is involved in the pathogenesis of conditions like rheumatoid arthritis and sepsis.
- Neurological disorders: It contributes to the inflammatory response in diseases such as stroke and spinal cord injury .
