Neuronal intracellular transport and neurodegenerative disease
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Santiago Ramón y Cajal's1 influential monographs in the late 1800s provided detailed neuronal morphology that first highlighted the complexity of axonal and dendritic environments. This morphologic complexity reflects the different cellular compartments with specialized function. The task of maintaining the neuronal morphologic structure and cellular subspecialization is required for the wide variety of neuronal functions. For example, in peripheral nerve, the functional integrity of an axon must be maintained over a length that may span a meter or more. In a single cortical neuron, thousands of dendritic spines must be constantly physically and physiologically remolded in order to provide the synaptic plasticity required for learning and memory. Supporting all these complex tasks is an elaborate neuronal intracellular transport system (NIT). The NIT is a highly regulated arrangement of cytoskeletal and motor proteins that allow bidirectional trafficking of proteins, organelles, and macromolecules (most of which are manufactured in the cell body) to their appropriate targets throughout the neuron. Recent genetic and molecular advances have demonstrated that the extreme demands on the NIT within the elaborate neurites may cause it to fail early in several disorders of the central and peripheral nervous system, and that this early failure may be a decisive step in disease expression.2,3 Furthermore, the position of the NIT as a critical shared pathway in neurologic disease makes for potential therapeutic interventions. In this focused review, we highlight examples that illustrate how the NIT plays a key role in neurodegenerative diseases.
THE MOLECULAR MACHINERY OF NEURONAL INTRACELLULAR TRANSPORT
Many of the molecular details of the NIT are known (figure). Cellular traffic throughout the cell relies on an elaborate cytoskeletal scaffold, studded with a variety of protein motors that utilize adenosine triphosphate (ATP) as fuel, and which shuttle the cargo. To ensure that the specific cargo is delivered to the precise intracellular microenvironment, …
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Letters: Rapid online correspondence
- Neuronal intracellular transport and neurodegenerative disease
- Steven R Brenner, Physician, St. Louis University Dept. Neurology & PsychiatrySBren20979@aol.com
- none
Submitted August 08, 2011 - Reply from the authors
- Nathan P. Staff, Assistant Professor of Neurology, Mayo Clinicstaff.nathan@mayo.edu
- Eduardo E. Benarroch, Christopher J. Klein
Submitted August 08, 2011
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