Abstract
Rho-associated protein kinase (ROCK) is a serine-threonine kinase originally identified as a crucial regulator of actin cytoskeleton. Recent studies have defined new functions of ROCK as a critical component of diverse signaling pathways in neurons. In addition, inhibition of ROCK causes several biological events such as increase of neurite outgrowth, axonal regeneration, and activation of prosurvival Akt. Thus, it has attracted scientist’s strong attentions and considered ROCK as a promising therapeutic target for the treatment of neurodegenerative disorders including Alzheimer disease, Parkinson’s disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, ROCK has two highly homologous isoforms, ROCK1 and ROCK2. Accumulated evidences indicate that ROCK1 and ROCK2 might involve in distinct cellular functions in central nervous system (CNS) and neurodegenerative processes. This review summarizes recent updates regarding ROCK isoformspecific functions in CNS and the progress of ROCK inhibitors in preclinical studies for neurodegenerative diseases.
Keywords: Axonal regeneration, central nervous system, fasudil, isoforms, LIMK, neurodegenerative diseases, rock.
Current Drug Targets
Title:ROCK in CNS: Different Roles of Isoforms and Therapeutic Target for Neurodegenerative Disorders
Volume: 18 Issue: 4
Author(s): Cheong-Meng Chong, Nana Ai and Simon Ming-Yuen Lee
Affiliation:
Keywords: Axonal regeneration, central nervous system, fasudil, isoforms, LIMK, neurodegenerative diseases, rock.
Abstract: Rho-associated protein kinase (ROCK) is a serine-threonine kinase originally identified as a crucial regulator of actin cytoskeleton. Recent studies have defined new functions of ROCK as a critical component of diverse signaling pathways in neurons. In addition, inhibition of ROCK causes several biological events such as increase of neurite outgrowth, axonal regeneration, and activation of prosurvival Akt. Thus, it has attracted scientist’s strong attentions and considered ROCK as a promising therapeutic target for the treatment of neurodegenerative disorders including Alzheimer disease, Parkinson’s disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, ROCK has two highly homologous isoforms, ROCK1 and ROCK2. Accumulated evidences indicate that ROCK1 and ROCK2 might involve in distinct cellular functions in central nervous system (CNS) and neurodegenerative processes. This review summarizes recent updates regarding ROCK isoformspecific functions in CNS and the progress of ROCK inhibitors in preclinical studies for neurodegenerative diseases.
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Cite this article as:
Chong Cheong-Meng, Ai Nana and Lee Ming-Yuen Simon, ROCK in CNS: Different Roles of Isoforms and Therapeutic Target for Neurodegenerative Disorders, Current Drug Targets 2017; 18 (4) . https://dx.doi.org/10.2174/1389450117666160401123825
DOI https://dx.doi.org/10.2174/1389450117666160401123825 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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