The proline-directed serine threonine kinase, Cdk5, is an unusual molecule that belongs to the well-known large family of proteins, cyclin-dependent kinases (Cdks). While it has significant homology with the mammalian Cdk2 and yeast cdc2, unlike the other Cdks, it has little role to play in cell cycle regulation and is activated by non-cyclin proteins, p35 and p39. It phosphorylates a spectrum of proteins, most of them associated with cell morphology and motility. A majority of known substrates of Cdk5 are cytoskeletal elements, signalling molecules or regulatory proteins. It also appears to be an important player in cell-cell communication. Highly conserved, Cdk5 is most abundant in the nervous system and is of special interest to neuroscientists as it appears to be indispensable for normal neural development and function. In normal cells, transcription and activity of Cdk5 is tightly regulated. Present essentially in post-mitotic neurons, its normal activity is obligatory for migration and differentiation of neurons in developing brain. Deregulation of Cdk5 has been implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. Regulators of Cdk5 activity are considered as potential therapeutic molecules for degenerative diseases. This review focuses on the role of Cdk5 in neural cells as regulator of cytoskeletal elements, axonal guidance, membrane transport, synaptogenesis and cell survival in normal and pathological conditions.
Neuroblastoma (NB) cell lines are transformed, neural crest derived cells, capable of unlimited proliferation in vitro. These cell lines retain the ability of differentiation into neuronal cell types on treatment with various agents. This ability of NB cells to proliferate as well as to differentiate makes it an excellent in vitro system for various studies. This review article focuses on the applications and potential uses of murine and human NB cell lines. NB cells are extensively used for testing neurotoxicity of putative drugs such as antimalarial or anticancer agents. NB cell lines have wide applications in virus research to understand various aspects of virus-host cell interactions at the molecular and cellular levels. They have been used to dissect the relationships between proliferation, differentiation and apoptosis. This feature has been useful in understanding the pediatric cancer--neuroblastoma and for development of newer therapies.
The neuropathies of the peripheral, central and autonomic nervous systems are known to be caused by hyperglycemia, a consequence of the deregulation of glucose in diabetes. Several in vivo models such as streptozotocin-induced diabetic rats, mice and Chinese hamsters have been used to study the pathogenesis of diabetic neuropathy because of their resemblance to human pathology. However, these in vivo models have met with strong ethical oppositions. Further, the system complexity has inherent limitations of inconvenience of analyzing ephemeral molecular events and crosstalk of signal transduction pathways. Alternative in vitro models have been selected and put to effective use in diabetic studies. We critically review the use of these in vitro models such as primary cultures of dorsal root ganglia, Schwann cells and neural tissue as well as neural cell lines which have proved to be excellent systems for detailed study. We also assess the use of embryo cultures for the study of hyperglycemic effects on development, especially of the nervous system. These systems function as useful models to scrutinize the molecular events underlying hyperglycemia-induced stress in neuronal systems and have been very effectively used for the same. This comprehensive overview of advantages and disadvantages of in vitro systems that are currently in use will be of interest especially for comparative assessment of results and for appropriate choice of models for experiments in diabetic neuropathy.
Novel clinical strategies need to be evolved, as pathogens, especially the ones that infect the human, develop resistance. To do so, host pathogen biology needs to be clearly understood and this can be done using a nematode worm, Caenorhabditis elegans, which harbours the same virulent microbes. Over several decades, the worm has been used to study host-microbe interaction with reference to immune response of the worm, antimicrobial molecules secreted, cell death in the worm body, quorum sensing network of the bacteria and fast or slow worm death. This mini review gives a bird's eye view of the directions that have been taken in these areas to date. Currently, the worm has been proposed to be an ideal model for high throughput screening of natural and synthetic drugs against a variety of bacteria. Experimental systems that allow this screening have been patented. Caenorhabditis elegans, thus, is one of the very effective models for studying pathogens that infect human.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.