Small Molecule Cyclin-Dependent Kinase Inhibitors Protect Against Neuronal Cell Death in the Ischemic-Reperfused Rat Retina

2011 ◽  
Vol 27 (5) ◽  
pp. 419-425 ◽  
Author(s):  
Kenji Sakamoto ◽  
Kayo Ohki ◽  
Maki Saito ◽  
Tsutomu Nakahara ◽  
Kunio Ishii
Keyword(s):  
Cell Death ◽  
Small Molecule ◽  
Kinase Inhibitors ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cyclin Dependent Kinase ◽  
Rat Retina

scholarly journals Defining the Kv2.1–syntaxin molecular interaction identifies a first-in-class small molecule neuroprotectant

2019 ◽  
Vol 116 (31) ◽  
pp. 15696-15705 ◽  
Author(s):  
Chung-Yang Yeh ◽  
Zhaofeng Ye ◽  
Aubin Moutal ◽  
Shivani Gaur ◽  
Amanda M. Henton ◽  
...  
Keyword(s):  
Cell Death ◽  
Small Molecule ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rational Approach ◽  
Tissue Slices ◽  
Intrinsically Disordered ◽  
C Terminus ◽  
A Cell

The neuronal cell death-promoting loss of cytoplasmic K+ following injury is mediated by an increase in Kv2.1 potassium channels in the plasma membrane. This phenomenon relies on Kv2.1 binding to syntaxin 1A via 9 amino acids within the channel intrinsically disordered C terminus. Preventing this interaction with a cell and blood-brain barrier-permeant peptide is neuroprotective in an in vivo stroke model. Here a rational approach was applied to define the key molecular interactions between syntaxin and Kv2.1, some of which are shared with mammalian uncoordinated-18 (munc18). Armed with this information, we found a small molecule Kv2.1–syntaxin-binding inhibitor (cpd5) that improves cortical neuron survival by suppressing SNARE-dependent enhancement of Kv2.1-mediated currents following excitotoxic injury. We validated that cpd5 selectively displaces Kv2.1–syntaxin-binding peptides from syntaxin and, at higher concentrations, munc18, but without affecting either synaptic or neuronal intrinsic properties in brain tissue slices at neuroprotective concentrations. Collectively, our findings provide insight into the role of syntaxin in neuronal cell death and validate an important target for neuroprotection.

Roles of cyclin-dependent kinase 4 and p53 in neuronal cell death induced by doxorubicin on cerebellar granule neurons in mouse

2004 ◽  
Vol 365 (3) ◽  
pp. 180-185 ◽  
Author(s):  
Yuko Otsuka ◽  
Tomoaki Tanaka ◽  
Daigaku Uchida ◽  
Yoshihiko Noguchi ◽  
Naokatsu Saeki ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cerebellar Granule Neurons ◽  
Granule Neurons ◽  
Cyclin Dependent Kinase ◽  
Cerebellar Granule

Protective effect of all-trans retinoic acid on NMDA-induced neuronal cell death in rat retina

2010 ◽  
Vol 635 (1-3) ◽  
pp. 56-61 ◽  
Author(s):  
Kenji Sakamoto ◽  
Masahide Hiraiwa ◽  
Maki Saito ◽  
Tsutomu Nakahara ◽  
Yoji Sato ◽  
...  
Keyword(s):  
Cell Death ◽  
Retinoic Acid ◽  
Protective Effect ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Rat Retina ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid
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