A mutation in dynein rescues axonal transport defects and extends the lifespan of ALS mice.

Kieran, Dairin, Hafezparast, Majid, Bohnert, Stephanie, Dick, James R T, Martin, Joanne, Schiavo, Giampietro, Fisher, Elizabeth M C and Greensmith, Linda (2005) A mutation in dynein rescues axonal transport defects and extends the lifespan of ALS mice. Journal of Cell Biology, 169 (4). pp. 561-7. ISSN 0021-9525

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Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative condition characterized by motoneuron degeneration and muscle paralysis. Although the precise pathogenesis of ALS remains unclear, mutations in Cu/Zn superoxide dismutase (SOD1) account for ~2025% of familial ALS cases, and transgenic mice overexpressing human mutant SOD1 develop an ALS-like phenotype. Evidence suggests that defects in axonal transport play an important role in neurodegeneration. In Legs at odd angles (Loa) mice, mutations in the motor protein dynein are associated with axonal transport defects and motoneuron degeneration. Here, we show that retrograde axonal transport defects are already present in motoneurons of SOD1G93A mice during embryonic development. Surprisingly, crossing SOD1G93A mice with Loa/+ mice delays disease progression and significantly increases life span in Loa/SOD1G93A mice. Moreover, there is a complete recovery in axonal transport deficits in motoneurons of these mice, which may be responsible for the amelioration of disease. We propose that impaired axonal transport is a prime cause of neuronal death in neurodegenerative disorders such as ALS.

Item Type: Article
Additional Information: This paper identified retrograde axonal transport pathway as a target for delaying disease onset in motor neuron disease. MH carried out biochemical analyses of brain and spinal cords in this study. This research was a collaborative study between MH and laboratories of L. Greensmith, G. Schiavo, and E.M.C. Fisher.
Schools and Departments: School of Life Sciences > Neuroscience
Depositing User: Majid Hafezparast
Date Deposited: 06 Feb 2012 18:49
Last Modified: 26 Mar 2012 12:53
URI: http://sro.sussex.ac.uk/id/eprint/18481
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