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


METHODS
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.
Lowry
K S
KS
Department of Anatomy and Cell Biology, Monash University, Clayton, Victoria, Australia.
Murray
S S
SS
McLean
C A
CA
Talman
P
P
Mathers
S
S
Lopes
E C
EC
Cheema
S S
SS
D019943:Amino Acid Substitution / Q000235:genetics; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase