Clusterin is a Chaperone protein involved in lipid transport, protein folding, and neurodegeneration. Associated with Alzheimer's disease and other age-related diseases.
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.
| Property |
Value |
| 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 |
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 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 - 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
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 interaction - Clusterin binds Aβ and promotes its clearance
- Neuroprotection - Reduced clusterin levels correlate with increased Aβ burden
- Therapeutic target - Enhancing clusterin is being explored as AD therapy
- Mutant huntingtin promotes clusterin aggregation
- Clusterin may help clear mutant huntingtin 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
Clusterin is widely expressed in the brain:
- Highest expression: Hippocampus, cortex, basal ganglia, cerebellum
- Moderate expression: Brainstem, thalamus
- Cellular localization: Cytosol, secretory vesicles, extracellular space
- Cell types: Neurons, astrocytes, microglia, oligodendrocytes
The Allen Brain Atlas shows high CLU expression in:
- Hippocampal pyramidal and granule cells
- Cortical pyramidal neurons
- Cerebellar Purkinje cells
- Harold et al., Clusterin and Alzheimer disease (2009)
- DeMattos et al., Clusterin as Aβ chaperone (2002)
- Miller et al., CLU variants and neurodegeneration (2013)
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.
- Pulst et al., SCA2 identification (1996)
- Elden et al., ATXN2 expansions in ALS (2010)
- Bhattacharjee et ATXN2 in RNA metabolism (2011)
- Last et al., Ataxin-2 function and disease (2020)
- Sato et al., ATXN2 in Parkinson's disease (2019)
- Gispert-Sanchez et al., ATXN2 and RNA granules (2015)
- Nonis et al., ATXN2 in diabetes (2022)
- Kumar et al., ATXN2 therapeutic targeting (2021)