Journal of neurochemistry
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Journal of neurochemistry · Jul 2016
Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury.
Traumatic brain injury (TBI) is associated with adverse effects on brain functions, including sensation, language, emotions and/or cognition. Therapies for improving outcomes following TBI are limited. A better understanding of the pathophysiological mechanisms of TBI may suggest novel treatment strategies to facilitate recovery and improve treatment outcome. ⋯ Moreover, TBI deregulates Ca(2+) -homeostasis triggering p25 production. The protein kinase Cdk5 is aberrantly activated by p25 leading to phosphorylation of substrates including tau and Rb protein. Loss of Cdk5 attenuates TBI lesion size, indicating that Cdk5 is a critical player in TBI pathogenesis and thus may be a suitable therapeutic target for TBI.
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Journal of neurochemistry · Jul 2016
Simvastatin inhibits neural cell apoptosis and promotes locomotor recovery via activation of Wnt/β-catenin signaling pathway after spinal cord injury.
Statins exhibit neuroprotective effects after spinal cord injury (SCI). However, the molecular mechanism underlying these effects remains unknown. This study demonstrates that the hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin (Simv) exhibits neuroprotective effects on neuronal apoptosis and supports functional recovery in a rat SCI model by activating the Wnt/β-catenin signaling pathway. ⋯ We verified the neuroprotective properties associated with simvastatin following spinal cord injury (SCI). Simvastatin reduced neuronal apoptosis, improved the functional and pathological recovery via activating Wnt/β-catenin signal pathway, however, the anti-apoptosis effects of simvastatin were reversed following suppressing Wnt/β-catenin signaling pathway in primary spinal cord neurons. The significant findings may provide clinical therapeutic value of simvastatin for treating SCI.