| CD33 — Cluster of Differentiation 33 | |
|---|---|
| Symbol | CD33 |
| Full Name | Cluster of Differentiation 33 (Siglec-3) |
| Chromosome | 19q13.41 |
| NCBI Gene | 945 |
| Ensembl | ENSG00000105383 |
| OMIM | 159590 |
| UniProt | P20138 |
| Diseases | Alzheimer's Disease, Acute Myeloid Leukemia |
| Expression | Myeloid cells, Microglia, Monocytes |
Cd33 Gene 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, also known as Siglec-3) is a gene located on chromosome 19q13.41 that encodes a sialic acid-binding immunoglobulin-like lectin (siglec)[1]. Genetic variants in CD33 are associated with altered risk of late-onset Alzheimer's Disease[2]. The gene is catalogued as NCBI Gene ID 945.
CD33 is primarily expressed on myeloid cells and microglia, where it plays important roles in immune regulation and has been implicated in Alzheimer's disease pathogenesis through modulation of neuroinflammation and amyloid clearance[3]. The protein is a member of the siglec family, which are cell surface receptors that recognize sialic acid residues on glycoproteins and glycolipids[1:1].
The CD33 gene encodes a transmembrane glycoprotein belonging to the siglec family of sialic acid-binding lectins[4]. The protein contains an extracellular V-type immunoglobulin-like domain that binds sialylated glycans, and an intracellular ITIM (immunoreceptor tyrosine-based inhibition motif) that transduces inhibitory signals[1:2].
CD33 is composed of several structural domains:
CD33 modulates immune responses through several mechanisms:
In the central nervous system, CD33 is expressed primarily on microglia and participates in:
CD33 variants are significantly associated with late-onset Alzheimer's disease. GWAS have identified specific single nucleotide polymorphisms (SNPs) in the CD33 gene that modify AD risk[2:1][7]:
The mechanism by which CD33 variants influence AD risk involves:
CD33 is a clinically important therapeutic target in acute myeloid leukemia (AML)[11]:
CD33 shows population-specific allele frequencies:
CD33 expression is highly cell-type specific:
CD33 represents a therapeutic target for both Alzheimer's disease and acute myeloid leukemia:
Current research on CD33 focuses on:
The study of Cd33 Gene 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.
Crocker, P.R., et al. (2007). Siglecs and their roles in the immune system. Nature Reviews Immunology. PMID:17344856. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Naj, A.C., et al. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. Nature Genetics. PMID:21460841. ↩︎ ↩︎ ↩︎
Griciuc, A., et al. (2013). Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron. PMID:23644516. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Freeman, S.D., et al. (1995). Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules. Blood. PMID:7612125. ↩︎ ↩︎ ↩︎ ↩︎
Bradshaw, E.M., et al. (2013). CD33 Alzheimer's disease locus: altered monocyte function and amyloid biology. Nature Neuroscience. PMID:23603548. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Sokolowski, J.D., et al. (2014). Modulation of synaptic development and plasticity by siglecs. Frontiers in Cellular Neuroscience. PMID:25426030. ↩︎
Hollingworth, P., et al. (2011). Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with Alzheimer's disease. Nature Genetics. PMID:21460840. ↩︎ ↩︎
Bertram, L., et al. (2013). CD33 in Alzheimer's disease. Molecular Neurobiology. PMID:23907557. ↩︎ ↩︎ ↩︎
Malik, M., et al. (2015). CD33 genetic variability and Alzheimer's disease. Journal of Alzheimer's Disease. PMID:25860820. ↩︎ ↩︎
Raj, T., et al. (2014). Polarization of macrophages in Alzheimer's disease. Acta Neuropathologica Communications. PMID:25406568. ↩︎ ↩︎ ↩︎
Larson, R.A. & Sievers, E.L. (2005). Gemtuzumab ozogamicin: a targeted therapy for AML. Cancer Chemotherapy and Pharmacology. PMID:15959728. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Walter, R.B., et al. (2012). Role of CD33 in normal and leukemic hematopoiesis. Blood. PMID:22715162. ↩︎ ↩︎ ↩︎