[HTML][HTML] Deregulation of PKN1 activity disrupts neurofilament organisation and axonal transport
C Manser, A Stevenson, S Banner, J Davies, EL Tudor… - FEBS letters, 2008 - Elsevier
C Manser, A Stevenson, S Banner, J Davies, EL Tudor, Y Ono, PN Leigh, DM McLoughlin…
FEBS letters, 2008•ElsevierNeurofilaments 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 …
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 …
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.
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