HSP90AB1 Protein

HSP90AB1 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">HSP90AB1 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>HSP90AB1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>HSP90AB1</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=HSP90AB1" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">150 edges</a></td>
</tr>
</table>

Hsp90Ab1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@hsp2022]
title: HSP90AB1 Protein (Heat shock protein HSP 90-beta) [@hsp2023]
category: protein [@targeting2022]

Overview [@hsp2023a]

HSP90AB1 Protein

Introduction

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">HSP90AB1 Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>HSP90AB1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>HSP90AB1</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=HSP90AB1" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">150 edges</a></td>
</tr>
</table>

Hsp90Ab1 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

--- [@hsp2022]
title: HSP90AB1 Protein (Heat shock protein HSP 90-beta) [@hsp2023]
category: protein [@targeting2022]

Overview [@hsp2023a]

This page provides comprehensive information about the subject's role in neurodegenerative diseases. The subject participates in various molecular pathways and cellular processes relevant to Alzheimer's disease, Parkinson's disease, and related conditions.

Basic Information

Protein Name: Heat shock protein HSP 90-beta Gene: HSP90AB1 UniProt ID: P08238 PDB Structures: 1BYQ, 2CG7 Molecular Weight: ~90 kDa Subcellular Localization: Cytoplasm

Structure

HSP90AB1 shares structural similarity with HSP90AA1 but has distinct features:

• N-terminal Domain: ATP binding pocket, highly conserved
• Middle Domain: Client protein binding and hydrolysis
• C-terminal Domain: Dimerization with EEVD motif

• Lacks certain post-translational modification sites
• Has different client protein preferences
• More constitutive expression in many tissues

Normal Function

Chaperone Activity

HSP90AB1 functions as a molecular chaperone with roles in:

• Protein folding: Assists in proper folding of nascent and stress-denatured proteins
• Quality control: Targets misfolded proteins for degradation
• Complex assembly: Facilitates multi-protein complex formation

Client Proteins

HSP90AB1 regulates client proteins including:

• Transcription factors: Glucocorticoid receptor, estrogen receptor
• Kinases: AKT, ERK, RAF family
• E3 ligases: CHOP, FBXW7
• Neuronal proteins: Synaptic receptors, ion channels

Neuronal Function

In [neurons](/entities/neurons) specifically:

• Synaptic protein maintenance: HSP90AB1 helps maintain synaptic receptor stability
• Axonal transport: Associates with transport machinery
• Response to oxidative stress: Protects neurons from [ROS](/entities/reactive-oxygen-species) damage
• Dendritic spine morphology: Regulates actin cytoskeleton

Role in Neurodegeneration

Alzheimer's Disease

HSP90AB1 involvement in AD:

• Amyloid pathology: Modulates [amyloid precursor protein](/entities/app-protein) (APP) processing and [Aβ](/proteins/amyloid-beta) generation
• [Tau](/proteins/tau) pathology: Associates with phosphorylated tau in affected neurons
• Synaptic failure: Loss of synaptic HSP90AB1 contributes to synaptic dysfunction
• Neuronal resilience: Higher HSP90AB1 expression correlates with neuronal resilience

Parkinson's Disease

In PD pathogenesis:

• [α-synuclein](/proteins/alpha-synuclein) interactions: Modulates α-synuclein aggregation propensity
• Mitochondrial function: Protects against mitochondrial toxins
• LRRK2 stability: Cooperates with HSP90AA1 in LRRK2 folding
• Dopaminergic neuron survival: Essential for dopaminergic neuron viability

Amyotrophic Lateral Sclerosis

HSP90AB1 in ALS:

• [TDP-43](/mechanisms/tdp-43-proteinopathy) pathology: Regulates TDP-43 aggregation through co-chaperone network
• Stress granule dynamics: Modulates stress granule formation
• Mutant SOD1: Assists in mutant SOD1 folding and clearance
• RNA metabolism: Client proteins include RNA-binding proteins

Huntington's Disease

In HD:

• Mutant huntingtin: Modulates aggregation of mutant [huntingtin protein](/proteins/huntingtin)
• Transcriptional dysregulation: Affects transcriptional regulators
• Neuronal dysfunction: Loss of protective function

Therapeutic Implications

HSP90 Inhibitors

Both HSP90AA1 and HSP90AB1 are targeted by HSP90 inhibitors:

• Geldanamycin derivatives: 17-AAG, 17-DMAG
• Purine analogs: PU-H71, BIIB028
• Resorcinol derivatives: AT13387, NVP-HSP990

Brain-Penetrant Inhibitors

• NVP-HSP990: Good brain penetration
• PU-H71: Accumulates in tumors and brain
• Apatorsen (OGX-427): Antisense oligonucleotide

Neuroprotective Approaches

• Up-regulation strategies: Increase HSP90AB1 expression
• Co-chaperone modulation: Target specific co-chaperones
• Combination approaches: With [autophagy](/entities/autophagy) inducers or抗氧化剂

Interactions

Co-chaperone Network

HSP90AB1 works with:

• HSP70 (HSPA1A): Primary co-chaperone
• HSP40 (DNAJA1): Co-chaperone for substrate loading
• HOP (STIP1): Adapter molecule
• AHA1: ATPase activator
• CDC37: Kinase-specific co-chaperone

Protein Complexes

• Glucocorticoid receptor complex: Classic steroid receptor complex
• AKT signaling complex: For AKT activation
• IKK complex: [NF-κB](/entities/nf-kb) activation

Summary

HSP90AB1 is a constitutively expressed molecular chaperone essential for neuronal protein homeostasis. While structurally similar to HSP90AA1, it has distinct client protein preferences and physiological roles. Both isoforms are implicated in neurodegenerative diseases, making them attractive therapeutic targets. However, the complexity of the HSP90 network and systemic toxicity of inhibitors remain significant challenges.

Background

The study of Hsp90Ab1 Protein 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

• [Neurodegenerative Diseases - Overview of disease category](/diseases/neurodegeneration)
• [Cell Types - Index of cell type pages](/cell-types)
• [Genes - Index of gene pages](/genes)
• [Proteins - Index of protein pages](/proteins)
• [Mechanisms - Index of mechanism pages](/mechanisms)