Galectins are a group of proteins found throughout the body, playing diverse roles in biological processes. Widespread across organisms, from primitive sponges to humans, they have conserved functions. Their ability to interact with specific sugar structures makes them important players in communication networks within and between cells, influencing various aspects of health.
What Galectins Are and How They Work
Galectins are a family of proteins defined by their ability to bind to beta-galactoside sugars, often found on cell surfaces or within the extracellular matrix. This binding occurs through a specialized carbohydrate recognition domain (CRD). Humans have identified 15 different galectins, each encoded by a specific LGALS gene.
These proteins can be found both inside cells, in the cytosol or nucleus, and outside cells in the extracellular space. Their interaction with cells resembles a “key and lock” mechanism, where the galectin binds to specific sugar “locks” on other molecules. This binding is calcium-independent, unlike other lectin families. Depending on their structure, galectins can have one or two CRDs, allowing them to form dimers or pentamers. This enables them to cross-link multiple sugar-containing molecules and create signaling platforms.
Galectins’ Roles in Normal Body Functions
Galectins contribute to maintaining normal physiological processes. They are involved in regulating the immune system, where they can either promote or suppress inflammatory responses depending on the specific galectin, the inflammatory stimulus, and the cellular environment. For instance, galectin-1 and galectin-9 can mediate the programmed death of T cells. This is important for clearing activated and infected T cells after an immune response and preventing self-reactive T cells from circulating.
Beyond immunity, galectins influence cellular processes such as cell growth, differentiation, and programmed cell death (apoptosis). Galectin-7, for example, participates in epithelial maintenance by regulating cell growth, differentiation, and apoptosis. They also play a role in cell adhesion and migration, helping cells to stick together or move within tissues, which is important for tissue formation and repair. Galectin-3, for instance, can influence cell-matrix adhesion by interacting with integrins, which are cell surface receptors. Galectins contribute to tissue homeostasis by maintaining the balance and proper functioning of various organs and systems.
Galectins’ Involvement in Disease
When the normal regulation or expression of galectins is disrupted, they can contribute to the development and progression of various diseases. In cancer, certain galectins can promote tumor growth, spread (metastasis), and resistance to therapies. For example, galectin-3 can enhance tumor invasion and metastasis by facilitating the clustering of integrins and signaling pathways related to cell adhesion. Galectin-1 has been linked to impaired immune surveillance in cancer by inducing the programmed death of T-cells, potentially reducing the effectiveness of some cancer treatments.
Galectins are also implicated in inflammatory and autoimmune conditions. Their ability to either promote or dampen inflammation means that an imbalance in their activity can contribute to chronic inflammation, as seen in conditions like arthritis. Galectin-3, for instance, is considered a pro-inflammatory molecule, and its elevated levels correlate with inflammation and fibrosis in various conditions, including autoimmune diseases. Galectins can also contribute to fibrotic diseases, involving excessive scar tissue formation in organs such as the lungs, liver, and heart. Galectin-1 activates fibroblasts, leading to collagen deposition and tissue remodeling that accelerates disease progression in these organs.
Galectins as Therapeutic Targets
Understanding the roles of galectins in disease has opened avenues for developing new therapeutic strategies. Scientists are exploring ways to manipulate galectin activity to treat various diseases. By designing molecules that can specifically block galectin binding to their sugar targets, researchers aim to inhibit their disease-promoting functions.
One approach involves developing inhibitors that prevent galectins from interacting with their ligands. For example, carbohydrate-based drugs like belapectin (GR-MD-02) are being investigated as galectin-3 inhibitors to treat conditions like non-alcoholic steatohepatitis (MASH) cirrhosis and certain cancers. Other strategies include using galectins themselves as delivery vehicles for drugs. These efforts highlight the promise of targeting galectins for treating conditions ranging from cancer to autoimmune disorders and fibrotic diseases.