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A potential role for the p75 low-affinity neurotrophin receptor in spinal motor neuron degeneration in murine and human amyotrophic lateral sclerosis.

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  • 1Department of Anatomy and Cell Biology, Monash University, Clayton, Victoria, Australia.

Abstract

INTRODUCTION:

The p75 neurotrophin receptor has been recognized as a death-signalling molecule under certain circumstances. Its role in motor neuron degeneration in amyotrophic lateral sclerosis (ALS) was analysed in SOD1-G93A transgenic mice and in spinal cords from human amyotrophic lateral sclerosis.

METHOD:

The precise loss of motor neurons in SOD1-G93A transgenic mice from birth to adulthood was established using the unbiased fractionator/optical dissector neuronal counting technique.

RESULTS:

This study showed an early trend in the loss of lumbar motor neurons in SOD1-G93A mice, beginning at birth and progressing to a massive 80% reduction by 4 months of age, when the disease is severe. This study also found that the p75 neurotrophin receptor was expressed in lumbar motor neurons in symptomatic SOD1-G93A mice and in motor neurons in the cervical spinal cords of patients with ALS.

CONCLUSIONS:

The murine and human ALS data suggest that the p75 neurotrophin receptor may play a death-signalling role in the pathogenesis of motor neuron degeneration. The precise mechanism by which this receptor drives the apoptotic process, both in murine SOD1-G93A motor neuron degeneration and in human amyotrophic lateral sclerosis, remains to be determined.

PMID:
11771768
[PubMed - indexed for MEDLINE]
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