Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions.

Abstract	Recent studies suggest that increased activity of cyclin-dependent kinase 5 (Cdk5) may contribute to neuronal death and cytoskeletal abnormalities in Alzheimer's disease. We report here such deregulation of Cdk5 activity associated with the hyperphosphorylation of tau and neurofilament (NF) proteins in mice expressing a mutant superoxide dismutase (SOD1(G37R)) linked to amyotrophic lateral sclerosis (ALS). A Cdk5 involvement in motor neuron degeneration is supported by our analysis of three SOD1(G37R) mouse lines exhibiting perikaryal inclusions of NF proteins. Our results suggest that perikaryal accumulations of NF proteins in motor neurons may alleviate ALS pathogenesis by acting as a phosphorylation sink for Cdk5 activity, thereby reducing the detrimental hyperphosphorylation of tau and other neuronal substrates.
Authors	M D Nguyen, R C Larivière, J P Julien
Journal	Neuron (Neuron) Vol. 30 Issue 1 Pg. 135-47 (Apr 2001) ISSN: 0896-6273 [Print] United States
PMID	11343650 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Nerve Tissue Proteins Neurofilament Proteins neuronal Cdk5 activator (p25-p35) tau Proteins Superoxide Dismutase Cyclin-Dependent Kinase 5 Cdk5 protein, mouse Cyclin-Dependent Kinases
Topics	Amyotrophic Lateral Sclerosis (enzymology, pathology, physiopathology) Animals Cell Compartmentation (physiology) Cyclin-Dependent Kinase 5 Cyclin-Dependent Kinases (metabolism) Disease Models, Animal Fluorescent Antibody Technique Inclusion Bodies (metabolism) Longevity (genetics) Mice Mice, Knockout (abnormalities, metabolism) Motor Neurons (enzymology, pathology) Mutation (physiology) Nerve Degeneration (enzymology, pathology, physiopathology) Nerve Tissue Proteins (metabolism) Neurofilament Proteins (metabolism) Phosphorylation Superoxide Dismutase (genetics, metabolism) tau Proteins (metabolism)

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