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A chemical compound commonly used to inhibit PKR, {8‐(imidazol‐4‐ylmethylene)‐6H‐azolidino[5,4‐g] benzothiazol‐7‐one}, protects neurons by inhibiting cyclin‐dependent kinase by Hsin‐Mei Chen; Lulu Wang; Santosh R. D’Mello is a Neuroscience article available to read on EtoBox.

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## Abstract Activation of the double‐stranded RNA‐dependent protein kinase (PKR) has been implicated in the pathogenesis of several neurodegenerative diseases. We find that a compound widely used as a pharmacological inhibitor of this enzyme, referred to as PKR inhibitor (PKRi), {8‐(imidazol‐4‐ylmethylene)‐6H‐azolidino[5,4‐g]benzothiazol‐7‐one}, protects against the death of cultured cerebellar granule and cortical neurons. PKRi also prevents striatal neurodegeneration and improves behavioral outcomes in a chemically induced mouse model of Huntington’s disease. Surprisingly, PKRi fails to block the phosphorylation of eIF2α, a downstream target of PKR, and does not reduce the autophosphorylation of PKR enzyme immunoprecipitated from neurons. Furthermore, neurons lacking PKR are fully protected from apoptosis by PKRi, demonstrating that neuroprotection by this compound is not mediated by PKR inhibition. Using __in vitro__ kinase assays we investigated whether PKRi affects any other protein kinase. These analyses demonstrated that PKRi has no major inhibitory effect on pro‐apoptotic kinases such as the c‐Jun N‐terminal kinases, the p38 MAP kinases and the death‐associated protein kina

Who reads A chemical compound commonly used to inhibit PKR, {8‐(imidazol‐4‐ylmethylene)‐6H‐azolidino[5,4‐g] benzothiazol‐7‐one}, protects neurons by inhibiting cyclin‐dependent kinase?

Author

Hsin‐Mei Chen; Lulu Wang; Santosh R. D’Mello

Publisher

Wiley

Published

2008

Language

EN

Field

Neuroscience (Life Sciences)