Intraneuronal Transport and Defense Mechanisms with Possible Pathogenetic Relevance in Huntington’s Disease (HD)

Abstract

AbstractNeurons are extremely polarized cells with a complex and unique morphology, as well as long processes (axon and dendrites) that extend far away from the nerve cell body. This architectonic feature of polarization with afferent (i.e., dendrites) and efferent processes (i.e., axons) requires efficient communication between the body of nerve cells and their periphery and makes nerve cells particularly dependent on functionally intact, sufficient, and timely axonal and/or dendritic intracellular transport processes over long distances. These intra-axonal trafficking processes guarantee bidirectional transport of subcellular compartments, including membrane organelles to or from the nerve cell processes, and enable the supply for specific action sites in the axon (e.g., nodes of Ranvier, axon terminal, synapses) and the disposal of vital cell organelles, membrane structures, synaptic vesicles, soluble neuronal proteins, or ion channels. Therefore, these targeted intraneuronal transport processes represent an essential prerequisite for the survival of the nerve cells of the human brain. The functional maintenance of nerve cells depends largely on the sufficient, locally correct, and precisely timed anterograde axonal transport of proteins and cell organelles from the cell body. In addition, the proper nerve cell function requires the retrograde trafficking of worn-out cell organelles back from the terminal regions to the cell body (Fig. 8.1) (De Vos et al. 2008; Gunawardena and Goldstein 2005; Li and Conforti 2013; Millecamps and Julien 2013). Long-range microtubule-based transport of cargos is the main mechanism (1) to deliver and target cellular components, organelles, and proteins from the cell body to their peripheral action site and/or (2) to remove them in the case of exhaustion. This long-range microtubule-based transport is accomplished by two major components: (1) “engines” or main microtubule-based molecular motors (i.e., kinesin, dynein) which need energy from ATP hydrolysis to move cargos along the microtubule cytoskeletal tracks and (2) neuronal microtubules, which represent the “rails” on which molecular motors loaded with cargos can run. Microtubules are very important in a number of cellular processes and are involved in maintaining the structure of the cell and, together with microfilaments and intermediate filaments as well as microtubules, form the cytoskeleton within the nerve cell’s cytoplasm. Neuronal microtubules are long, hollow cylinders made up of polymerized α- and β-tubulin dimers, are among the core structures of the neuronal cytoskeleton, and are crucial for the maintenance of its structure as well as for organizing motility and transport of intracellular constituents. Microtubule-associated proteins (MAP) like the cytoskeletal protein tau bind to and stabilize neuronal microtubules, promote their correct polymerization and assembly, and maintain their structural integrity. Neuronal microtubules are highly dynamic structures capable to undergo rapid periods of growth and shrinkage to generate force and enable the motor proteins kinesin and dynein to transport neuronal organelles and other cellular components, as well as neuronal proteins (Fig. 8.1) (De Vos et al. 2008; Gunawardena and Goldstein 2005; Li and Conforti 2013; Millecamps and Julien 2013).KeywordsNerve CellMolecular ChaperoneAxonal TransportMolecular MotorPostmitotic Nerve CellThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.