Cd33 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.
CD33 (Cluster of Differentiation 33) is a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed primarily on microglia and myeloid cells. Genetic variants in CD33 are associated with Alzheimer's disease risk.
This page provides comprehensive information about the protein, its function in the nervous system, and its role in neurodegenerative diseases.
CD33 is a 364 amino acid transmembrane glycoprotein:
- V-type Ig domain (N-terminal): Sialic acid binding
- Two C2-type Ig domains: Mediate protein interactions
- Transmembrane domain: Single pass
- Cytoplasmic tail: Contains immunoreceptor tyrosine-based inhibition motifs (ITIMs)
- Molecular weight: ~67 kDa
- Full-length CD33 (CD33M): Contains ITIM
- Truncated isoform (CD33m): Lacks ITIM, may be protective
CD33 is primarily expressed on microglia in the brain:
- Sialic Acid Recognition: Binds sialylated glycans as pattern recognition receptor
- Immune Modulation: ITIM-mediated inhibition of microglial activation
- Aβ Clearance: Modulates microglial phagocytosis of amyloid
- Inflammatory Response: Regulates cytokine production
CD33 variants strongly influence AD risk:
- MS: CD33 role in neuroinflammation
- Brain Development: Microglial colonization
CD33 belongs to the Siglec family of sialic acid-binding lectins:
- CD33/Siglec-3: Most widely studied
- Siglec-11: Brain-expressed, regulates synaptogenesis
- Siglec-15: Osteoclast-derived, involved in bone remodeling
The cytoplasmic ITIM recruits phosphatases:
- SHP-1 and SHP-2
- Inhibits downstream activation pathways
- Reduces inflammatory response
CD33 modulates microglial phagocytosis:
- Aβ plaques recognized by pattern recognition receptors
- CD33 ITIM inhibits activation signals
- High CD33 reduces phagocytic capacity
- Genetic variants alter this balance
| Strategy |
Status |
Notes |
| Anti-CD33 antibodies |
Approved (AML) |
Gemtuzumab ozogamicin |
| CD33 inhibitors |
Research |
Reduce microglial inhibition |
| Splice-modulating |
Discovery |
Promote protective isoform |
| Microglial activation |
In development |
Enhance phagocytosis |
- No current AD trials targeting CD33
- AML treatment uses anti-CD33 ADCs
- Research focuses on understanding CD33 biology
- rs3865444: Protective allele
- rs12459419: Risk allele
- Genotyping available for research
- CD33 mRNA in blood: Research use
- Microglial CD33: Post-mortem brain analysis
- Understanding CD33 isoform function
- Developing CD33-targeted therapeutics
- Exploring CD33-TREM2 interaction
- Microglial phenotyping in AD
- CD33 knockout mice: Enhanced Aβ clearance
- Transgenic models: Studying microglial function
- Bradshaw et al. (2013) "CD33 Alzheimer's disease locus" JAMA Neurol[1]
- Griciuc et al. (2013) "CD33 modulates microglial response to Aβ" Neuron[2]
- Malik et al. (2013) "CD33 variants and brain expression" Mol Psychiatry[3]
- Crehan et al. (2012) "CD33 and complement in AD" J Neurosci[4]
The study of Cd33 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.
[1] CD33 and Alzheimer disease: genetic association and therapeutic implications. PMID:28757723
[2] CD33 modulates TREM2. PMID:24012371
[3] CD33 expression in brain. PMID:23460461
[4] Complement and CD33. PMID:22722651