CLU Gene - Clusterin

CLU Gene - Clusterin

Overview

Clusterin is a Chaperone protein involved in lipid transport, protein folding, and neurodegeneration. Associated with [Alzheimer's disease](/diseases/alzheimers-disease) and other age-related diseases.

title: CLU Gene [@bhattacharjee2011]

--- [@last2020]

CLU (Clusterin)

Introduction

Clu Gene Clusterin is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@sato2019]

<div class="infobox infobox-gene"> [@gispertsanchez2015]

| Property | Value | [@nonis2022]
|----------|-------| [@kumar2021]
| Gene Symbol | CLU |
| Full Name | Clusterin |
| Chr Location | 8p21.1 |
| NCBI Gene ID | 1115 |
| OMIM ID | 185551 |
| Ensembl ID | ENSG00000120885 |
| UniProt ID | P10909 |
| Encoded Protein | Clusterin (ApoJ) |
| Associated Diseases | Alzheimer's disease, Huntington's disease, ALS, frontotemporal dementia |

</div>

Function

CLU encodes clusterin, also known as apolipoprotein J (ApoJ), a multifunctional glycoprotein that is highly expressed in the brain. Clusterin participates in various physiological processes including lipid transport, complement regulation, and apoptosis.

...

CLU Gene - Clusterin

Overview

Clusterin is a Chaperone protein involved in lipid transport, protein folding, and neurodegeneration. Associated with [Alzheimer's disease](/diseases/alzheimers-disease) and other age-related diseases.

title: CLU Gene [@bhattacharjee2011]

--- [@last2020]

CLU (Clusterin)

Introduction

Clu Gene Clusterin is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@sato2019]

<div class="infobox infobox-gene"> [@gispertsanchez2015]

| Property | Value | [@nonis2022]
|----------|-------| [@kumar2021]
| Gene Symbol | CLU |
| Full Name | Clusterin |
| Chr Location | 8p21.1 |
| NCBI Gene ID | 1115 |
| OMIM ID | 185551 |
| Ensembl ID | ENSG00000120885 |
| UniProt ID | P10909 |
| Encoded Protein | Clusterin (ApoJ) |
| Associated Diseases | Alzheimer's disease, Huntington's disease, ALS, frontotemporal dementia |

</div>

Function

CLU encodes clusterin, also known as apolipoprotein J (ApoJ), a multifunctional glycoprotein that is highly expressed in the brain. Clusterin participates in various physiological processes including lipid transport, complement regulation, and apoptosis.

Key normal physiological functions include:

• Cholesterol transport - Lipoprotein particle formation and lipid homeostasis
• Complement inhibition - Regulates complement cascade activation
• [Apoptosis](/entities/apoptosis) regulation - Inhibits caspase-dependent and independent cell death
• Protein aggregation - Molecular chaperone that prevents protein misfolding
• Synaptic protection - Supports synaptic function and plasticity
• [Blood-brain barrier](/entities/blood-brain-barrier) - Involved in BBB maintenance and repair

The protein has two subunits:

• Alpha chain (1-205) - Contains complement-binding regions
• Beta chain (206-449) - Chaperone activity domain

Disease Associations

Alzheimer's Disease (AD)

CLU is one of the most significant genetic risk factors for late-onset AD:

• GWAS significance - CLU rs11136000 polymorphism associated with reduced AD risk
• [Aβ](/proteins/amyloid-beta) interaction - Clusterin binds [Aβ](/proteins/amyloid-beta) and promotes its clearance
• Neuroprotection - Reduced clusterin levels correlate with increased Aβ burden
• Therapeutic target - Enhancing clusterin is being explored as AD therapy

Huntington's Disease (HD)

• Mutant [huntingtin](/proteins/huntingtin-protein) promotes clusterin aggregation
• Clusterin may help clear mutant [huntingtin](/genes/htt) aggregates
• Altered expression in HD brains

ALS and FTD

• Clusterin inclusions found in motor neurons of ALS patients
• Elevated clusterin in cerebrospinal fluid of ALS patients
• Genetic variants may modify disease progression

Expression

Clusterin is widely expressed in the brain:

• Highest expression: [Hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex), basal ganglia, cerebellum
• Moderate expression: Brainstem, thalamus
• Cellular localization: Cytosol, secretory vesicles, extracellular space
• Cell types: [Neurons](/entities/neurons), [astrocytes](/entities/astrocytes), [microglia](/entities/microglia), oligodendrocytes

The Allen Brain Atlas shows high CLU expression in:

• Hippocampal pyramidal and granule cells
• Cortical pyramidal neurons
• Cerebellar Purkinje cells

Key Publications

[Harold et al., Clusterin and Alzheimer disease (2009)](https://doi.org/10.1016/j.ajhg.2009.12.004)

[DeMattos et al., Clusterin as Aβ chaperone (2002)](https://doi.org/10.1073/pnas.212641299)

[Miller et al., CLU variants and neurodegeneration (2013)](https://doi.org/10.1016/j.neurobiolaging.2012.11.026)

Background

The study of Clu Gene Clusterin 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.

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
• [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
• [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

Cross-links

• Clusterin Protein
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Huntington's Disease](/diseases/huntingtons)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)

References

[Pulst et al., SCA2 identification (1996) (1996)](https://doi.org/10.1056/NEJM199601043340104)

[Elden et al., ATXN2 expansions in ALS (2010) (2010)](https://doi.org/10.1038/nature09320)

[Unknown, Bhattacharjee et ATXN2 in RNA metabolism (2011) (2011)](https://doi.org/10.1093/hmg/ddr236)

[Last et al., Ataxin-2 function and disease (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32877654/)

[Sato et al., ATXN2 in Parkinson's disease (2019) (2019)](https://pubmed.ncbi.nlm.nih.gov/30681783/)

[Gispert-Sanchez et al., ATXN2 and RNA granules (2015) (2015)](https://pubmed.ncbi.nlm.nih.gov/25823658/)

[Nonis et al., ATXN2 in diabetes (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/35061024/)

[Kumar et al., ATXN2 therapeutic targeting (2021) (2021)](https://pubmed.ncbi.nlm.nih.gov/34011045/)

Pathway Context

Pathway Diagram

The following diagram shows the key molecular relationships involving CLU Gene - Clusterin discovered through SciDEX knowledge graph analysis: