Axon degeneration: mechanisms and consequences

Broom, Lucy J. and Perry, V. Hugh (2010) Axon degeneration: mechanisms and consequences. In, Feldmeyer, Dirk and Lübke, Joachim H.R. (eds.) New Aspects of Axonal Structure and Function. Springer New York, NY, pp. 181-207. (doi:10.1007/978-1-4419-1676-1_10).

Abstract

Historically the focus of research into neurodegenerative diseases has been the cell body, but more recently this is shifting to acknowledge the strong contribution of axon and synapse degeneration to neurodegenerative diseases. Axonal loss is evident in traumatic injury of the spinal cord as well as neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and toxic neuropathy. For example, end stage multiple sclerosis plaques show up to 60% loss of axons and the extent of axonal damage is most pronounced in active demyelinating plaques, although demyelination is not a prerequisite for axonal injury. This suggests that axonal loss is an early event in disease pathology and contributes to the functional deficits experienced by the patient. While therapeutic interventions which protect the cell body in models of spinal cord injury, ALS and MS do show some efficacy ameliorating clinical symptoms, directing protection to the axon may prove to be of considerable value. However, this requires a greater understanding of axonal biology, the extent to which the axon can function as an independent cellular compartment under normal physiological conditions, and also the pathways that are involved in the initiation of degeneration.

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