Calbindin - Calbindin D-28k

title: Calbindin - Calbindin D-28k
category: protein

Calbindin D-28k

Introduction

Calbindin Calbindin D 28K is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@german1992]

<div class="infobox infobox-protein"> [@iacopino1992]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Calbindin D-28k</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Calbindin</td></tr>
<tr><td><strong>Gene</strong></td><td><a href="/genes/calb1">CALB1</a></td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P05937">P05937</a></td></tr>
<tr><td><strong>PDB ID</strong></td><td>1IG5</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>30 kDa</td></tr>
<tr><td><strong>Localization</strong></td><td>Cytosol</td></tr>
<tr><td><strong>Protein Family</strong></td><td>EF-hand calcium-binding proteins</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">10 edges</a></td>
</tr>
</table>
</div>

Overview

...

title: Calbindin - Calbindin D-28k
category: protein

Calbindin D-28k

Introduction

Calbindin Calbindin D 28K is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@german1992]

<div class="infobox infobox-protein"> [@iacopino1992]
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">Calbindin D-28k</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Calbindin</td></tr>
<tr><td><strong>Gene</strong></td><td><a href="/genes/calb1">CALB1</a></td></tr>
<tr><td><strong>UniProt ID</strong></td><td><a href="https://www.uniprot.org/uniprot/P05937">P05937</a></td></tr>
<tr><td><strong>PDB ID</strong></td><td>1IG5</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>30 kDa</td></tr>
<tr><td><strong>Localization</strong></td><td>Cytosol</td></tr>
<tr><td><strong>Protein Family</strong></td><td>EF-hand calcium-binding proteins</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/inflammation" style="color:#ef9a9a">Inflammation</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">10 edges</a></td>
</tr>
</table>
</div>

Overview

Calbindin D-28k (encoded by the [CALB1](/genes/calb1) gene) is a calcium-binding protein of the EF-hand family with a molecular weight of approximately 30 kDa. It is widely expressed in [neurons](/cell-types/neurons) throughout the central nervous system, particularly in [Purkinje cells](/cell-types/purkinje-cells) of the [cerebellum](/brain-regions/cerebellum), [hippocampal](/brain-regions/hippocampus) pyramidal [neurons](/entities/neurons), and various [cortical](/anatomy/cerebral-cortex) neuronal populations.

Calbindin serves as a high-affinity calcium buffer, protecting neurons from calcium overload and excitotoxicity. It is one of the most studied calcium-binding proteins in the context of [neurodegeneration](/diseases/neurodegeneration).

Structure

Calbindin D-28k possesses:

• 6 EF-hand calcium-binding motifs
• High-affinity calcium binding (Kd ~10^-7 M)
• Characteristic EF-hand protein fold
• Dimerization capability
• Structure solved by X-ray crystallography (PDB: 1IG5)

Normal Function

Calcium Buffering

Calbindin functions as a neuroprotective calcium buffer:

• Protects neurons from excitotoxicity
• Modulates intracellular calcium kinetics
• Prevents mitochondrial calcium overload
• Shapes synaptic plasticity

Neuronal Protection

Calbindin provides neuroprotection through:

• Buffering excessive calcium influx
• Regulating calcium-dependent signaling pathways
• Protecting against oxidative stress
• Maintaining mitochondrial function

Synaptic Plasticity

Calbindin modulates synaptic function:

• Regulates [long-term potentiation](/mechanisms/long-term-potentiation) (LTP)
• Affects synaptic vesicle cycling
• Influences GABAergic signaling
• Modulates network oscillations

Role in Neurodegenerative Diseases

Alzheimer's Disease

Calbindin D-28k has been extensively studied in [Alzheimer's disease](/diseases/alzheimers-disease):

• Early Marker: Loss of calbindin is an early marker of neuronal dysfunction
• Selective Vulnerability: Calbindin+ neurons show relative resistance to [amyloid-beta](/proteins/amyloid-beta-protein) toxicity
• Mechanisms of Protection:
• Enhanced calcium homeostasis
• Reduced mitochondrial dysfunction
• Lower oxidative stress response
• Resistance to apoptotic signals
• Therapeutic Interest: Calbindin restoration is a potential therapeutic strategy

Parkinson's Disease

In [Parkinson's disease](/diseases/parkinsons-disease):

• Calbindin expression correlates with [dopaminergic](/cell-types/dopaminergic-neurons) neuron vulnerability
• Vulnerable [substantia nigra](/brain-regions/substantia-nigra) pars compacta neurons have low calbindin
• Calbindin+ neurons in the basal ganglia show relative preservation
• Potential role in [alpha-synuclein](/proteins/alpha-synuclein) pathology

Huntington's Disease

Calbindin alterations in [Huntington's disease](/diseases/huntington-disease):

• Reduced calbindin in striatal neurons
• Correlation with disease progression
• Affected medium spiny neuron populations

Other Neurodegenerative Conditions

• Amyotrophic Lateral Sclerosis (ALS): Variable expression changes
• Epilepsy: Altered calbindin in seizure models
• Stroke: Protective role in ischemic injury

Therapeutic Implications

Calbindin has significant therapeutic potential:

Gene Therapy: Viral delivery of CALB1 to protect neurons

Small Molecule Mimetics: Developing calbindin-mimetic compounds

Cell-Based Therapy: Transplantation of calbindin-expressing cells

Biomarker: Calbindin as a marker for neuronal health

Research Methods

Calbindin is widely used as a neuronal marker:

• Immunohistochemistry: Primary marker for specific neuron populations
• Transgenic Reporter Lines: For studying neuronal development
• Electrophysiology: Studying calcium dynamics in calbindin+ neurons
• Single-cell RNA-seq: Marker for neuronal classification

Interactions and Pathways

Calbindin interacts with:

• Calcium-dependent signaling proteins
• Mitochondrial calcium uniporter (MCU)
• Calmodulin-dependent kinases
• Transcription factors

Background

The study of Calbindin Calbindin D 28K has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

See Also

• [Gene: CALB1](/mechanisms/dopaminergic-neuron-vulnerability)
• [Cell Types: Calbindin Neurons](/cell-types)
• [Cell Types: Calbindin Neurons in Alzheimer's Disease](/cell-types)
• [Proteins: Calretinin (related EF](/proteins)
• [Proteins: Parvalbumin (related calcium](/proteins)
• [Mechanisms: Calcium Signaling in Neurodegeneration](/mechanisms)
• [Mechanisms: Excitotoxicity](/mechanisms)

External Links

• [UniProt: Calbindin D-28k (P05937)](https://www.uniprot.org/uniprot/P05937)
• [PDB: Calbindin Structure (1IG5)](https://www.ebi.ac.uk/pdbe/alpha/1IG5)
• [Human Protein Atlas: CALB1](https://www.proteinatlas.org/ENSG00000132563-CALB1)

References

[Baimbridge et al., (1992). Calbindin-D28k and calcium signaling. Prog Neurobiol (1992)](https://pubmed.ncbi.nlm.nih.gov/1570799/)

[Mattson et al., (1991). Calcium-binding protein neuroprotection. J Neurosci Res (1991)](https://pubmed.ncbi.nlm.nih.gov/1849954/)

[Unknown, Heizmann & Braun (1992). Calcium binding proteins. Trends Neurosci (1992)](https://doi.org/10.1016/0166-2236(92)

[Unknown, Winsky & Kuznicki (1995). Distribution of calbindin. J Comp Neurol (1995)](https://doi.org/10.1002/cne.903630310)

[German et al., (1992). Calbindin in substantia nigra. Exp Neurol (1992)](https://doi.org/10.1016/0014-4886(92)

[Iacopino et al., (1992). Calbindin and excitotoxicity. Brain Res Mol Brain Res (1992)](https://doi.org/10.1016/0169-328X(92)