. Cell cycle regulators in the neuronal death pathway of amyotrophic lateral sclerosis caused by mutant superoxide dismutase 1. J Neurosci. 2003 Mar 15;23(6):2131-40. PubMed.

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  1. This is a very interesting finding, and complements nicely the paper by Rideout et al., 2003. Our lab has also found (unpublished observations) activated cdk4 in the Nieman-Pick type C mouse model, which has an axonopathy resembling that of ALS. I find it very reasonable that more than one cdk might be involved in these neurodegenerative diseases. The Rb protein is the only characterized substrate for cdk4, but it is possible that the presence of an ectopic, active cdk in a neuron might lead to additional irregularities, including phosphorylation of substrates not normally acted upon by the enzyme. Such dysregulation would certainly affect neuronal function and contribute to death.

    References:

    . Cyclin-dependent kinase activity is required for apoptotic death but not inclusion formation in cortical neurons after proteasomal inhibition. J Neurosci. 2003 Feb 15;23(4):1237-45. PubMed.