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Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport.
- Source :
-
FEBS letters [FEBS Lett] 2008 Jun 25; Vol. 582 (15), pp. 2303-2308. Date of Electronic Publication: 2008 Jun 02. - Publication Year :
- 2008
-
Abstract
- Neurofilaments are synthesised in neuronal cell bodies and then transported through axons. Damage to neurofilament transport is seen in amyotrophic lateral sclerosis (ALS). Here, we show that PKN1, a neurofilament head-rod domain kinase is cleaved and activated in SOD1G93A transgenic mice that are a model of ALS. Moreover, we demonstrate that glutamate, a proposed toxic mechanism in ALS leads to caspase cleavage and disruption of PKN1 in neurons. Finally, we demonstrate that a cleaved form of PKN1 but not wild-type PKN1 disrupts neurofilament organisation and axonal transport. Thus, deregulation of PKN1 may contribute to the pathogenic process in ALS.
- Subjects :
- Amyotrophic Lateral Sclerosis etiology
Amyotrophic Lateral Sclerosis genetics
Animals
Caspase 3 metabolism
Disease Models, Animal
Glutamic Acid toxicity
Humans
Male
Mice
Mice, Transgenic
Neurons drug effects
Neurons enzymology
Neurons ultrastructure
Protein Kinase C genetics
Rats
Spinal Cord metabolism
Superoxide Dismutase genetics
Superoxide Dismutase-1
Amyotrophic Lateral Sclerosis enzymology
Axonal Transport genetics
Neurofilament Proteins metabolism
Neurofilament Proteins ultrastructure
Protein Kinase C metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0014-5793
- Volume :
- 582
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- FEBS letters
- Publication Type :
- Academic Journal
- Accession number :
- 18519042
- Full Text :
- https://doi.org/10.1016/j.febslet.2008.05.034