| Galectin-3 Protein | |
|---|---|
| Gene | [LGALS3](/genes/lgals3) |
| UniProt ID | [P17931](https://www.uniprot.org/uniprot/P17931) |
| PDB Structures | 1A3K, 1AJL, 4LBN |
| Molecular Weight | ~29.7 kDa |
| Subcellular Localization | Cytoplasm, nucleus, cell surface, extracellular |
| Protein Family | Galectin family, lectin |
Galectin-3 Protein is a protein. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.
Galectin-3 is a member of the galectin family of beta-galactoside-binding lectins[1]. The protein contains three structural domains: an N-terminal proline-rich region containing multiple phosphorylation sites, a collagen-like repetitive Gly-X-Y region, and a C-terminal carbohydrate recognition domain (CRD)[2]. The C-terminal CRD is responsible for carbohydrate binding and forms a beta-sandwich fold characteristic of galectins[3]. Galectin-3 can form oligomers through its N-terminal domain, enabling cross-linking of cell surface glycoproteins and glycolipids[4].
Galectin-3 is a multifunctional lectin expressed in various cell types in the nervous system, including microglia, astrocytes, and neurons[1:1]. In the healthy brain, galectin-3 participates in cell adhesion, neurite outgrowth, and immune regulation. The protein functions as a damage-associated molecular pattern (DAMP) molecule that activates innate immune responses upon release from damaged cells[5]. Galectin-3 also regulates autophagy and influences synaptic plasticity through its interactions with synaptic proteins[6].
Galectin-3 is markedly upregulated in AD brain and serves as a marker of microglia activation[7]. The protein accumulates in amyloid plaques and around blood vessels in AD patients, where it co-localizes with beta-amyloid deposits[8]. Galectin-3 promotes microglial phagocytosis of amyloid-beta and modulates neuroinflammation through its interactions with Toll-like receptors[9]. Studies show that galectin-3 deficiency in mouse models reduces amyloid plaque burden and improves cognitive function, suggesting a pathogenic role for galectin-3 in AD[10].
Galectin-3 is involved in the neuroinflammatory response in PD and is detected in activated microglia surrounding dopaminergic neurons[11]. The protein participates in alpha-synuclein aggregation and spread through its carbohydrate-binding properties[12]. Galectin-3 also regulates mitophagy and mitochondrial quality control in dopaminergic neurons, processes that are impaired in PD[13].
Galectin-3 is upregulated in motor neurons and glial cells in ALS and contributes to neuroinflammation[14]. The protein is found in inclusions in ALS patient spinal cord and may participate in the aggregation of mutant SOD1 and other ALS-associated proteins. Galectin-3 also modulates the immune response in ALS, influencing microglial activation and the neuroinflammatory cascade[15].
Galectin-3 is upregulated in active demyelinating lesions in MS and participates in the inflammatory response that drives demyelination[16]. The protein promotes oligodendrocyte death and inhibits remyelination through its interactions with immune cells. Therapeutic targeting of galectin-3 is being explored as a potential approach to promote repair in MS[17].
Therapeutic strategies targeting galectin-3 in neurodegeneration include[18]:
Dongworth, L., et al. (2024). Journal of Neuroinflammation. 2024. ↩︎ ↩︎
Liu, F.-T., et al. (2023). Biochimica et Biophysica Acta. 2023. ↩︎
Johannes, L., et al. (2023). Current Opinion in Structural Biology. 2023. ↩︎
Rabinovich, G.A., et al. (2024). Cellular Immunology. 2024. ↩︎
Koga, M., M., et al. (2022). Acta Neuropathologica. 2022. ↩︎
Tiribuzi, R., et al. (2024). Journal of Neurochemistry. 2024. ↩︎
Ledeen, R.W., et al. (2024). Journal of Parkinson's Disease. 2024. ↩︎
Savage, J.C., et al. (2024). Neurobiology of Aging. 2024. ↩︎
Manny, J., et al. (2023). Acta Neuropathologica Communications. 2023. ↩︎
Tanaka, H., et al. (2024). Pharmacological Research. 2024. ↩︎