Neuron-glia: understanding cellular copper homeostasis, its cross-talk and their contribution towards neurodegenerative diseases
文献信息
Ashima Bhattacharjee, Sandeepan Ghosh, Ajanta Chatterji, Kaustav Chakraborty
Over the years, the mechanism of copper homeostasis in various organ systems has gained importance. This is owing to the involvement of copper in a wide range of genetic disorders, most of them involving neurological symptoms. This highlights the importance of copper and its tight regulation in a complex organ system like the brain. It demands understanding the mechanism of copper acquisition and delivery to various cell types overcoming the limitation imposed by the blood brain barrier. The present review aims to investigate the existing work to understand the mechanism and complexity of cellular copper homeostasis in the two major cell types of the CNS – the neurons and the astrocytes. It investigates the mechanism of copper uptake, incorporation and export by these cell types. Furthermore, it brings forth the common as well as the exclusive aspects of neuronal and glial copper homeostasis including the studies from copper-based sensors. Glia act as a mediator of copper supply between the endothelium and the neurons. They possess all the qualifications of acting as a ‘copper-sponge’ for supply to the neurons. The neurons, on the other hand, require copper for various essential functions like incorporation as a cofactor for enzymes, synaptogenesis, axonal extension, inhibition of postsynaptic excitotoxicity, etc. Lastly, we also aim to understand the neuronal and glial pathology in various copper homeostasis disorders. The etiology of glial pathology and its contribution towards neuronal pathology and vice versa underlies the complexity of the neuropathology associated with the copper metabolism disorders.
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Metallomics
Metallomics publishes cutting-edge investigations aimed at elucidating the identification, distribution, dynamics, role and impact of metals and metalloids in biological systems. Studies that address the “what, where, when, how and why” of these inorganic elements in cells, tissues, organisms, and various environmental niches are welcome, especially those employing multidisciplinary approaches drawn from the analytical, bioinorganic, medicinal, environmental, biophysical, cell biology, plant biology and chemical biology communities. We are particularly interested in articles that enhance our chemical and/or physical understanding of the molecular mechanisms of metal-dependent life processes, and those that probe the common space between metallomics and other ‘omics approaches to uncover new insights into biological processes. Metallomics seeks to position itself at the forefront of those advances in analytical chemistry destined to clarify the enormous complexity of biological systems. As such, we particularly welcome those papers that outline cutting-edge analytical technologies, e.g., in the development and application of powerful new imaging, spectroscopic and mass spectrometric modalities. Work that describes new insights into metal speciation, trafficking and dynamics in complex systems or as a function of microenvironment are also strongly encouraged. Studies that examine the interconnectivity of metal-dependent processes with systems level responses relevant to organismal health or disease are also strongly encouraged, for example those that probe the effect of chemical exposure on metal homeostasis or the impact of metal-based drugs on cellular processes.
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