Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.

Gap junctions between glial cells or neurons are ubiquitously expressed in the mammalian brain and play a role in brain development including cell differentiation, cell migration and survival, and tissue homeostasis, as well as in human diseases including hearing loss, neuropathies, epilepsy, brain trauma, and cardiovascular disease. This volume provides neuroscience researchers and students with a single source for information covering the physiological, behavioral and pathophysiological roles of gap junctions in the brain. In addition, the book also discusses human disease conditions associated with mutations in single gap junction connexion genes, making it applicable to clinicians doing translational research. Finally, it includes reviews of pharmacological studies with gap junction blockers and openers, summarizing information obtained from phenotyping gap junctions mouse mutants. - Serves as the most current and comprehensive reference available covering the physiological, behavioral and pathophysiological roles of gap junctions in the brain - Chapters summarize knowledge of the basic physiology of gap junctions in the brain, as well as of human disease conditions associated with mutations in single gap junction connexin genes - Includes reviews of pharmacological studies with gap junction blockers and openers, summarizing information obtained from phenotyping gap junctions mouse mutants

This book discusses the primary functions of microtubule-associated proteins (MAPs) such as MAP2 and tau in neuronal morphogenesis, as well as relationships between neuronal differentiation and the expression of neuronal intermediate filaments (nestin, alpha internexin, and neurofilament triplet proteins). It emphasizes the importance of several cytoskeletal proteins for neuronal differentiation and morphogenesis, organelle transport, and synaptic functions. The book considers the involvement of tau MAPs in the formation of paired helical filaments in Alzheimer's disease, and it examines the mechanisms of organelle transports and molecular motors such as kinesin, braindynein, and kinesin superfamily proteins. Cytoskeletal proteins involved in synaptic formation and transmitter release and new synaptic junctional-associated proteins are explored as well.

Parkinson's disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Current PD medications treat symptoms; none halt or retard dopaminergic neuron degeneration. The main obstacle to developing neuroprotective therapies is a limited understanding of the key molecular mechanisms that provoke neurodegeneration. The discovery of PD genes has led to the hypothesis that misfolding of proteins and dysfunction of the ubiquitin-proteasome pathway are pivotal to PD pathogenesis. Previously implicated culprits in PD neurodegeneration, mitochondrial dysfunction, and oxidative stress may also act in part by causing the accumulation of misfolded proteins, in addition to producing other deleterious events in dopaminergic neurons. Neurotoxin-based models have been important in elucidating the molecular cascade of cell death in dopaminergic neurons. PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.

With the invitation to edit this volume, I wanted to take the opportunity to assemble reviews on different aspects of circadian clocks and rhythms. Although most c- tributions in this volume focus on mammalian circadian clocks, the historical int- duction and comparative clocks section illustrate the importance of various other organisms in deciphering the mechanisms and principles of circadian biology. Circadian rhythms have been studied for centuries, but only recently, a mole- lar understanding of this process has emerged. This has taken research on circadian clocks from mystic phenomenology to a mechanistic level; chains of molecular events can describe phenomena with remarkable accuracy. Nevertheless, current models of the functioning of circadian clocks are still rudimentary. This is not due to the faultiness of discovered mechanisms, but due to the lack of undiscovered processes involved in contributing to circadian rhythmicity. We know for example, that the general circadian mechanism is not regulated equally in all tissues of m- mals. Hence, a lot still needs to be discovered to get a full understanding of cir- dian rhythms at the systems level. In this respect, technology has advanced at high speed in the last years and provided us with data illustrating the sheer complexity of regulation of physiological processes in organisms. To handle this information, computer aided integration of the results is of utmost importance in order to d- cover novel concepts that ultimately need to be tested experimentally.

Cell senescence is the process whereby cells permanently lose the possibility to proliferate without undergoing cell death, and occurs in a plethora of distinct model organisms. In Cell Senescence: Methods and Protocols, expert researchers in the field detail the methods that are now commonly used to study cell senescence, in model organisms encompassing bacteria, fungi, worms, flies, zebrafish, and mammalian cells. These techniques cover the study of all the morphological, biochemical and functional manifestations of senescence at the cellular level and include protocols for population analyses and high-throughput approaches in suitable model organisms. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.

Tyrosine Kinase Inhibitors as Sensitizing Agents for Chemotherapy, the fourth volume in the Cancer Sensitizing Agents for Chemotherapy Series, focuses on strategic combination therapies that involve a variety of tyrosine kinase inhibitors working together to overcome multi-drug resistance in cancer cells. The book discusses several tyrosine kinase inhibitors that have been used as sensitizing agents, such as EGFR, BCR-ABL, ALK and BRAF. In each chapter, readers will find comprehensive knowledge on the inhibitor and its action, including its biochemical, genetic, and molecular mechanisms' emphases. This book is a valuable source for oncologists, cancer researchers and those interested in applying new sensitizing agents to their research in clinical practice and in trials. - Summarizes the sensitizing role of some tyrosine kinase inhibitors in existing research - Brings recent findings in several cancer types, both experimental and clinically, with a particular emphases on underlying biochemical, genetic, and molecular mechanisms - Provides an updated and comprehensive knowledge regarding the field of combinational cancer treatment