Cytoskeleton Of The Nervous System

This monograph begins with a general description of the cytoskeleton in axonal development and pathology and then moves to more detailed descriptions of particular components, including microtubules and associated proteins, neurofilaments and interacting proteins, actin and its binding proteins, and glial fibrillary acidic protein. The later chapters focus on the functional significance of the neuronal cytoskeleton in axonal transport and its regulation in health and disease states. The Cytoskeleton of the Nervous System will encourage further development of unifying principles and stimulate new conceptual and technical approaches toward a better understanding of cytoskeleton functions in health and disease.

The coordinated action of the different cytoskeletal polymers--microtubules, actin filaments and neurofilaments-- is essential for the establishment, remodeling and maintenance of neuronal architecture throughout the neuron lifetime. Neurons are among the most polarized cells, with a long thin axon and multiple thicker and shorter dendrites. Achieving this complex morphology, and the precise and accurate formation of an intricate network of synaptic contacts is critical for the proper transmission and reception of signals in the brain. Neuronal polarization precedes axon outgrowth and the subsequent differentiation of short neurites into dendrites, as part of the neuronal differentiation program that involves both intrinsic and extrinsic signals that converge at the cytoskeletal level. Growth cones, which are sensory and locomotor structures located at the tip of growing axons, are key elements in the transduction of extracellular cues into cytoskeletal changes, guiding axons to their right destinations. Neuronal migration, another crucial process during brain development, occurs in close coordination with neuronal differentiation. Migration involves as well an extensive rearrangement of neuronal cell shape that relies on cytoskeleton reorganization. Further processes, such as dendritic spine formation and growth, establishment of synaptic contacts or synaptic plasticity in mature neurons also depend on cytoskeletal dynamics. Fine-tune regulation of neuronal cytoskeleton is therefore crucial for the maintenance of neuronal integrity and functionality. Mutations in genes that code for cytoskeletal proteins often have deleterious effects in neurons, such as abnormal migration or differentiation, deficient axonal transport of organelles and synaptic vesicles, or impaired synaptic signaling. Several human Nervous System disorders, including neurodevelopmental, psychiatric, and neurodegenerative diseases, have been linked to cytoskeletal dysfunction. Cytoskeletal reorganization is also crucial to regulate nerve cell repair following Nervous System injury. Many of the pathways that control cell-intrinsic axon regeneration lead to axon cytoskeletal remodeling. Moreover, most extracellular cues that inhibit regeneration of damaged axons in Central Nervous System following traumatic injury or neurodegeneration, are known to modulate cytoskeletal dynamics and organization. Based on these findings, regulators of cytoskeleton dynamics have emerged as promising therapeutic targets in several brain disorders and in the context of regeneration of injured axons. Hence, remodeling of neuronal cytoskeleton underlies all the dramatic morphological changes that occur in developing and adult neurons. Understanding the specific molecular mechanisms that control cytoskeleton rearrangements in neurons is far from complete. This Frontiers Research Topic gathers a selection of articles focused on the diverse and key roles of cytoskeleton in neuronal biology.

This informative Neuromethods series book surveys the cytoskeleton, and offers detailed protocols on emerging techniques including in vivo and in vitro imaging and preparative strategies for isolation of cytoskeletal components of the central nervous system.

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.

Nanoneuroscience is the study of computationally relevant biomolecules found inside neurons. Because of recent technological advances at the nanometer scale, scientists have at their disposal increasingly better ways to study the brain and the biophysics of its molecules. This book describes how biomolecules contribute to the operations of synapses and perform other computationally relevant functions inside dendrites. These biomolecular operations considerably expand the brain-computer analogy - endowing each neuron with the processing power of a silicon-based multiprocessor. Amazingly, the brain contains hundreds of billions of neurons.

This text is an introduction to the interface between the actin cytoskeleton and the myriad of issues fundamental to the understanding of the nervous system. It covers the neurobiology of actin ranging from basic cellular organization and function to the roles of actin in the health and disease states of the nervous system. Its opening chapter presents the fundamental concepts required to appreciate the details of the molecular machinery that regulates actin in a cellular context, setting the stage for the first part of the book which reviews the neurobiology of actin at the cellular level. The latter section of the book then discusses the functions of actin in the context of neurobiological issues ranging from early development to synaptic function and disease states of the nervous system. This text is intended for neuroscientists interested in investigating the actin cytoskeleton in the context of their particular neuroscience research program, and its chapters are cross-referenced in order to assist readers in finding relevant information that is covered in greater depth in other chapters.