title: Rho Kinase and Dopaminergic Degeneration: A Promising Therapeutic Target for Parkinson's Disease.
abstract: The small GTP-binding protein Rho plays an important role in several cellular functions. RhoA, which is a member of the Rho family, initiates cellular processes that act on its direct downstream effector Rho-associated kinase (ROCK). ROCK inhibition protects against dopaminergic cell death induced by dopaminergic neurotoxins. It has been suggested that ROCK inhibition activates neuroprotective survival cascades in dopaminergic neurons. Axon-stabilizing effects in damaged neurons may represent another mechanism of neuroprotection of dopaminergic neurons by ROCK inhibition. However, it has been shown that microglial cells play a crucial role in neuroprotection by ROCK inhibition and that activation of microglial ROCK mediates major components of the microglial inflammatory response. Additional mechanisms such as interaction with autophagy may also contribute to the neuroprotective effects of ROCK inhibition. Interestingly, ROCK interacts with several brain factors that play a major role in dopaminergic neuron vulnerability such as NADPH-oxidase, angiotensin, and estrogen. ROCK inhibition may provide a new neuroprotective strategy for Parkinson's disease. This is of particular interest because ROCK inhibitors are currently used against vascular diseases in clinical practice. However, it is necessary to develop more potent and selective ROCK inhibitors to reduce side effects and enhance the efficacy.
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain joseluis.labandeira@usc.es.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Labandeira-Garcia
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Rodríguez-Perez
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Villar-Cheda
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Borrajo
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Dominguez-Meijide
authors.affiliation: Laboratory of Neuroanatomy and Experimental Neurology, Department of Morphological Sciences, CIMUS, University of Santiago de Compostela, Santiago de Compostela, Spain Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Guerra
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D009410:Nerve Degeneration / Q000188:drug therapy / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010300:Parkinson Disease / Q000188:drug therapy* / Q000201:enzymology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D018696:Neuroprotective Agents; D054460:rho-Associated Kinases
keywords: NADPH-oxidase; Parkinson; Rho kinase; angiotensin; estrogen; neuroprotection