Distinct Roles of ROCK1 and ROCK2 on the Cerebral Ischemia Injury and Subsequently Neurodegenerative Changes

Abstract

Cerebral ischemic injury is one of the main causes of adult disability and death. Although significant progress has been made, cerebral ischemia continues to be a major risk to public health worldwide. The Rho kinase (ROCK) signaling pathway has been reported to be significantly involved in many mechanisms of cerebral injury. Although ROCK is ubiquitously expressed in all tissues, ROCK2 subtype expression in brain and the spinal cord is more abundant and improves with age. This makes it a promising target for new therapeutic approaches. In this article, we review the current knowledge on the involvement of ROCK in cerebral ischemia injury and neurodegenerative changes after cerebral injury. After a detailed description of the mechanism of ROCK involvement in axonal regeneration and synaptic function, different roles of ROCK1 and ROCK2 in neurons under physiological and pathological conditions are compared and discussed. In addition, different functions of genetic and pharmacological inhibitions of ROCK1 and ROCK2 on cerebral injury are discussed.

CTNNAL1 participates in the regulation of mucus overproduction in HDM‐induced asthma mouse model through the YAP‐ROCK2 pathway

“…ROCK1 and ROCK2 have different functions in various types of cells and tissues. 47,48 In our study, when CTNNAL1 was silenced, the expression of ROCK1 decreased while ROCK2 increased both in vitro and in vivo. We found that CTNNAL1 deficiency significantly increased ROCK2 expression after HDM stimulation.…”

Integrative Computational Approach Revealed Crucial Genes Associated With Different Stages of Diabetic Retinopathy

“…Moving to genes altered in early stage of DR, except for one study on IGSF21 (Immunoglobin Superfamily Member 21) (Lin et al, 2016), none of the genes have been studied in context to DR. However, ROCK2 (Rho Associated Coiled-Coil Containing Protein Kinase 2) (Koch et al, 2014;Lu et al,…”

“…The identified early genes were found to be involved in one or more crucial events associated with DR progression like angiogenesis, oxidative stress, inflammation, etc. Further, some of the early genes like ROCK2 (Koch et al, 2014;Lu et al, 2020), UHRF1 (Ramesh et al, 2016), and MAPT (C. C. Zhang et al, 2016) are shown to participate in neurodegeneration, which is one of the earliest events in DR development. Also, in the present study, one of the identified early genes, i.e., NR1H4, was also found to be the target of one of the downregulated miRNAs (has-mir-192) identified in plasma sample of NPDR cases.…”

CREB Coactivator CRTC2 Plays a Crucial Role in Endothelial Function

“…p190RhoGAP is initially reported to RhoA negatively regulator and recently the dysregulation of RhoGAPs is thought to be related with CNS disease (Huang et al, 2017) and ROCK1 is downstream target of RhoA (Kümper et al, 2016;Lu et al, 2020).…”