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Published on: July 10, 2019
ROCKing Regeneration: Rho Kinase Inhibition as Molecular Target for Neurorestoration
Lars Tönges1, Jan-Christoph Koch, Mathias Bähr
1Department of Neurology, University Medicine Göttingen Göttingen, Germany.
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.
Insights
Rho-associated kinase (ROCK) inhibition shows promise for central nervous system (CNS) repair by enhancing nerve regeneration and cell survival after injury. Targeting ROCK pathways offers potential neurorestorative strategies for CNS trauma.
Area of Science:
- Neuroscience
- Regenerative Medicine
- Molecular Biology
Background:
- Central nervous system (CNS) regeneration is hindered by inhibitory signaling and poor cell survival post-injury.
- Rho-associated kinase (ROCK) is a key mediator of growth cone collapse and actin dynamics, inhibiting neurite outgrowth.
- Emerging evidence implicates ROCK in detrimental roles for cellular survival in the CNS.
Purpose of the Study:
- To review the multifaceted roles of ROCK in intracellular signaling beyond neurite growth inhibition.
- To focus on neurorestorative strategies targeting ROCK in CNS injury models, particularly neurotrauma.
- To evaluate pharmacological inhibitors and RNAi approaches for ROCK in preclinical and clinical studies.
Main Methods:
- Review of existing literature on ROCK signaling pathways in the CNS.
- Analysis of preclinical and clinical studies investigating ROCK inhibitors and RNAi.
- Evaluation of outcomes related to regenerative growth and cellular protection.
Main Results:
- ROCK participates in diverse intracellular signaling pathways impacting CNS repair.
- Pharmacological and RNAi-based strategies targeting ROCK demonstrate potential for promoting regeneration.
- ROCK inhibition shows promise for enhancing cellular survival in CNS injury contexts.
Conclusions:
- ROCK is a critical target for promoting CNS regeneration and cellular resilience.
- Targeting ROCK pathways offers a viable therapeutic avenue for neurorestorative approaches in CNS trauma.
- Further investigation into ROCK inhibition is warranted for clinical translation in CNS repair.
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