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Cytoskeleton, Axonal Transport, and the Mechanisms of Axonal Neuropathy

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Cytoskeleton of the Nervous System

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 3))

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Abstract

Axonal neuropathy, or axonopathy, is a major category of neuropathy in the central and peripheral nervous systems. Axonopathy is characterized by axonal degeneration and dysfunctional axonal transport. Peripheral axonopathies are more common than central axonopathies due to their lack of protection from the blood–brain barrier and resultant vulnerability to metabolic challenges. Although the pathogenic mechanisms of peripheral axonal neuropathy are still unclear, the dying-back pattern of the axonal damage suggests axons, rather than neuronal cell bodies, are the primary targets of the disease. Recent studies have revealed that defects of the cytoskeleton and axonal transport are associated with several types of peripheral neuropathy and some central neurological diseases. Direct evidence from genetic studies demonstrates that mutations in major components of the cytoskeleton and axonal transport result in axonal defects in several types of Charcot-Marie-Tooth disease, amyotrophic lateral sclerosis, Alzheimer disease, and other types of genetic neurological disorders. In addition, post-translational modifications of cytoskeleton proteins also result in axonal defects in metabolic diseases like diabetic neuropathy. In this condition, phosphorylation and excess glycation of the axonal cytoskeletal components induce abnormal axonal functions. Advanced glycation end products (AGEs) and their receptors are most likely responsible for the axonal dysfunction. Taken together, understanding the defects in the axonal cytoskeleton and transport mechanisms provides important information for developing new treatments to prevent cytoskeletal damage in axonal neuropathy.

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  1. Department of Neurology, University of Michigan, Ann Arbor, MI, 48109-2200, USA

    Hsinlin T. Cheng, Brian Callaghan, Jacqueline R. Dauch & Eva L. Feldman

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  1. Hsinlin T. Cheng
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  2. Brian Callaghan
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  3. Jacqueline R. Dauch
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  4. Eva L. Feldman
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Correspondence to Hsinlin T. Cheng .

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  1. Psychiatric Research, Nathan S. Kline Institute for, 140 Old Orangeburg Road, Orangeburg, 10962, New York, USA

    Ralph A. Nixon

  2. Psychiatric Research, Nathan S. Kline Institute for, 140 Old Orangeburg Road, Orangeburg, 10962, New York, USA

    Aidong Yuan

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Cheng, H.T., Callaghan, B., Dauch, J.R., Feldman, E.L. (2011). Cytoskeleton, Axonal Transport, and the Mechanisms of Axonal Neuropathy. In: Nixon, R., Yuan, A. (eds) Cytoskeleton of the Nervous System. Advances in Neurobiology, vol 3. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6787-9_27

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