ROCKing regeneration: Rho kinase inhibition as molecular target for neurorestoration
Open Access
- 1 January 2011
- journal article
- Published by Frontiers Media SA in Frontiers in Molecular Neuroscience
- Vol. 4, 39
- https://doi.org/10.3389/fnmol.2011.00039
Abstract
Regenerative failure in the CNS largely depends on pronounced growth inhibitory signaling and reduced cellular survival after a lesion stimulus. One key mediator of growth inhibitory signaling is Rho-associated kinase (ROCK), which has been shown to modulate growth cone stability by regulation of actin dynamics. Recently, there is accumulating evidence the ROCK also plays a deleterious role for cellular survival. In this manuscript we illustrate that ROCK is involved in a variety of intracellular signaling pathways that comprise far more than those involved in neurite growth inhibition alone. Although ROCK function is currently studied in many different disease contexts, our review focuses on neurorestorative approaches in the CNS, especially in models of neurotrauma. Promising strategies to target ROCK by pharmacological small molecule inhibitors and RNAi approaches are evaluated for their outcome on regenerative growth and cellular protection both in preclinical and in clinical studies.Keywords
This publication has 101 references indexed in Scilit:
- Targeting a Dominant Negative Rho Kinase to Neurons Promotes Axonal Outgrowth and Partial Functional Recovery After Rat Rubrospinal Tract LesionMolecular Therapy, 2009
- ROCK Isoform Regulation of Myosin Phosphatase and Contractility in Vascular Smooth Muscle CellsCirculation Research, 2009
- Promoting Axon Regeneration in the Adult CNS by Modulation of the PTEN/mTOR PathwayScience, 2008
- Identification of a nonkinase target mediating cytotoxicity of novel kinase inhibitorsMolecular Cancer Therapeutics, 2008
- Rho Kinase (ROCK) InhibitorsJournal of Cardiovascular Pharmacology, 2007
- Rho kinase in the regulation of cell death and survivalArchivum Immunologiae et Therapiae Experimentalis, 2007
- Rho-Kinase Inhibition Acutely Augments Blood Flow in Focal Cerebral Ischemia via Endothelial MechanismsJournal of Cerebral Blood Flow & Metabolism, 2006
- Can regenerating axons recapitulate developmental guidance during recovery from spinal cord injury?Nature Reviews Neuroscience, 2006
- Glial inhibition of CNS axon regenerationNature Reviews Neuroscience, 2006
- Specificity and mechanism of action of some commonly used protein kinase inhibitorsBiochemical Journal, 2000