Literature DB >> 11343650

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

M D Nguyen1, R C Larivière, J P Julien.   

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.

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Year:  2001        PMID： 11343650     DOI： 10.1016/s0896-6273(01)00268-9

Source DB:  PubMed          Journal:  Neuron        ISSN： 0896-6273            Impact factor:   17.173


  85 in total

1.  Sumoylation of p35 modulates p35/cyclin-dependent kinase (Cdk) 5 complex activity.

Authors:  Anja Büchner; Petranka Krumova; Sundar Ganesan; Mathias Bähr; Katrin Eckermann; Jochen H Weishaupt
Journal:  Neuromolecular Med       Date:  2014-11-13       Impact factor: 3.843

2.  Type II keratins are phosphorylated on a unique motif during stress and mitosis in tissues and cultured cells.

Authors:  Diana M Toivola; Qin Zhou; Luc S English; M Bishr Omary
Journal:  Mol Biol Cell       Date:  2002-06       Impact factor: 4.138

3.  Synaptic deficits are rescued in the p25/Cdk5 model of neurodegeneration by the reduction of β-secretase (BACE1).

Authors:  Paola Giusti-Rodríguez; Jun Gao; Johannes Gräff; Damien Rei; Takahiro Soda; Li-Huei Tsai
Journal:  J Neurosci       Date:  2011-11-02       Impact factor: 6.167

4.  A 24-residue peptide (p5), derived from p35, the Cdk5 neuronal activator, specifically inhibits Cdk5-p25 hyperactivity and tau hyperphosphorylation.

Authors:  Ya-Li Zheng; Niranjana D Amin; Ya-Fang Hu; Parvathi Rudrabhatla; Varsha Shukla; Jyotshnabala Kanungo; Sashi Kesavapany; Philip Grant; Wayne Albers; Harish C Pant
Journal:  J Biol Chem       Date:  2010-08-18       Impact factor: 5.157

5.  Non-aggregating tau phosphorylation by cyclin-dependent kinase 5 contributes to motor neuron degeneration in spinal muscular atrophy.

Authors:  Nimrod Miller; Zhihua Feng; Brittany M Edens; Ben Yang; Han Shi; Christie C Sze; Benjamin Taige Hong; Susan C Su; Jorge A Cantu; Jacek Topczewski; Thomas O Crawford; Chien-Ping Ko; Charlotte J Sumner; Long Ma; Yong-Chao Ma
Journal:  J Neurosci       Date:  2015-04-15       Impact factor: 6.167

6.  Cyclin-dependent kinase 5 is a mediator of dopaminergic neuron loss in a mouse model of Parkinson's disease.

Authors:  Patrice D Smith; Stephen J Crocker; Vernice Jackson-Lewis; Kelly L Jordan-Sciutto; Shawn Hayley; Matthew P Mount; Michael J O'Hare; Steven Callaghan; Ruth S Slack; Serge Przedborski; Hymie Anisman; David S Park
Journal:  Proc Natl Acad Sci U S A       Date:  2003-10-31       Impact factor: 11.205

7.  Cdk5 regulates the organization of Nestin and its association with p35.

Authors:  Cecilia M Sahlgren; Andrey Mikhailov; Samuli Vaittinen; Hanna-Mari Pallari; Hannu Kalimo; Harish C Pant; John E Eriksson
Journal:  Mol Cell Biol       Date:  2003-07       Impact factor: 4.272

8.  Amino acid sequence conservation of the algesic fragment of myelin basic protein is required for its interaction with CDK5 and function in pain.

Authors:  Andrei V Chernov; Albert G Remacle; Swathi K Hullugundi; Piotr Cieplak; Mila Angert; Jennifer Dolkas; Veronica I Shubayev; Alex Y Strongin
Journal:  FEBS J       Date:  2018-08-27       Impact factor: 5.542

Review 9.  Defective neurofilament transport in mouse models of amyotrophic lateral sclerosis: a review.

Authors:  Mala V Rao; Ralph A Nixon
Journal:  Neurochem Res       Date:  2003-07       Impact factor: 3.996

10.  Cyclin-dependent kinase inhibitors attenuate protein hyperphosphorylation, cytoskeletal lesion formation, and motor defects in Niemann-Pick Type C mice.

Authors:  Min Zhang; Jin Li; Paramita Chakrabarty; Bitao Bu; Inez Vincent
Journal:  Am J Pathol       Date:  2004-09       Impact factor: 4.307
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