Understanding nerve degeneration in spastic paraplegia

Hereditary spastic paraplegia (HSP) encompasses a group of neurodegenerative diseases characterized by progressive weakness, spasticity, and diverse patterns of inheritance, which is caused by degeneration of nerve axons. Elena Rugarli and colleagues from the Telethon Institute of Genetics and Medicine in Naples, Italy, developed a mouse model for studying HSP due to mutations in the Spg7 gene, which encodes the enzyme paraplegin. Paraplegin-deficient mice were affected by axonal swelling from failed axon transport, and axon degeneration. Long before this swelling ocurred the authors observed abnormalities in mitochondrial shape within nerve terminals that correlated with the onset of motor skill impairment. The number of axons containing these abnormal mitochondria was far greater than the number of swollen and degenerate axons. The authors suggest that local failure of mitochondrial function may affect axonal transport and cause axonal degeneration.

In an accompanying commentary, Harris Gelbard from the University of Rochester discusses a hypothetical scheme for altered mitochondrial function that may result from the loss of paraplegin activity, which may account for the pathology observed in Spg7-/- mice. A timely therapeutic intervention may therefore prevent axonal loss.

TITLE: Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport

AUTHOR CONTACT:
Elena Rugarli
Telethon Institute of Genetics and Medicine, Castellino, Naples, Italy.
Phone: 39-081-6132221
Fax: 39-081-5609877
E-mail: rugarli@tigem.it

View the PDF of this article at: http://www.jci.org/cgi/content/full/113/2/231

ACCOMPANYING COMMENTARY: Synapses and Sisyphus: life without paraplegin

AUTHOR CONTACT:
Harris A. Gelbard
University of Rochester Medical Center, Rochester, New York, USA.
Phone: (585) 273-1473
Fax: (585) 506-1947
E-mail: Harris_Gelbard@urmc.rochester.edu

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