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.
journal_name
Neuronjournal_title
Neuronauthors
Nguyen MD,Larivière RC,Julien JPdoi
10.1016/s0896-6273(01)00268-9subject
Has Abstractpub_date
2001-04-01 00:00:00pages
135-47issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(01)00268-9journal_volume
30pub_type
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