Zinc-dependent cellular pathways

Zinc-dependent cellular pathways refer to the diverse set of biological processes that utilize zinc as an essential structural or catalytic cofactor for thousands of proteins, including enzymes, transcription factors, and signaling molecules [NIH Office of Dietary Supplements, 2022]. These pathways are fundamental to cellular homeostasis, regulating gene expression through zinc-finger motifs and facilitating signal transduction in response to physiological stimuli [Kambe et al., 2015]. Dysregulation of zinc-mediated signaling is associated with a wide range of diseases, including various cancers where zinc transporters are often aberrantly expressed, and neurodegenerative conditions like Alzheimer's disease where zinc imbalance promotes protein aggregation [Sensi et al., 2009]. In the gastrointestinal tract, zinc-dependent pathways are crucial for maintaining the epithelial barrier, often acting through the inhibition of pro-inflammatory NF-κB signaling and calpain-mediated protein degradation [Miyoshi et al., 2023]. Therapeutic interventions targeting these pathways include zinc supplementation to address deficiencies, the use of chelators to manage metal toxicity, and the development of inhibitors for zinc-dependent enzymes such as histone deacetylases (HDACs) and matrix metalloproteinases (MMPs) [Ho, 2004]. Given the ubiquity of zinc in the proteome, these pathways represent a broad but critical area for drug discovery and nutritional intervention [Maret, 2013].

Other names

Zinc-mediated signalingZinc-dependent signaling pathwaysZinc homeostasis pathwaysZinc signaling

Modulation of zinc-dependent enzyme activity, regulation of zinc transporter expression, and chelation of intracellular zinc ions to alter signaling cascades [Ho, 2004; Maret, 2013].