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parkinso* AND (Rho kinase OR rock)

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https://www.readbyqxmd.com/read/29621594/rock-inhibition-in-models-of-neurodegeneration-and-its-potential-for-clinical-translation
#1
REVIEW
Jan Christoph Koch, Lars Tatenhorst, Anna-Elisa Roser, Kim-Ann Saal, Lars Tönges, Paul Lingor
Neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis are affecting a rapidly increasing population worldwide. While common pathomechanisms such as protein aggregation, axonal degeneration, dysfunction of protein clearing and an altered immune response have been characterized, no disease-modifying therapies have been developed so far. Interestingly, a significant involvement of the Rho kinase (ROCK) signaling pathway has been described in all of these mechanisms making it a promising target for new therapeutic approaches...
April 2, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29456132/csf-lamp2-concentrations-are-decreased-in-female-parkinson-s-disease-patients-with-lrrk2-mutations
#2
Andrea C Klaver, Mary P Coffey, Jan O Aasly, David A Loeffler
Lysosome-associated membrane glycoprotein 2 (lamp2) plays critical roles in chaperone-mediated autophagy (CMA) and macroautophagy. Its isoform lamp2a is decreased in Parkinson's disease (PD) substantia nigra. Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most known common cause of late-onset PD; although LRRK2 is thought to regulate macroautophagy, the influence of LRRK2 mutations on lamp2 concentrations in the CNS is unknown. To examine this issue we compared lamp2 levels in cerebrospinal fluid (CSF) between sporadic PD (sPD) patients (n = 31), LRRK2 PD patients (n = 20), and healthy control subjects with or without LRRK2 mutations (LRRK2 CTL = 30, CTL = 27)...
March 15, 2018: Brain Research
https://www.readbyqxmd.com/read/29448133/exposure-to-the-rock-inhibitor-fasudil-promotes-gliogenesis-of-neural-stem-cells-in-vitro
#3
Zubair Ahmed Nizamudeen, Lisa Chakrabarti, Virginie Sottile
Fasudil is a clinically approved Rho-associated protein kinase (ROCK) inhibitor that has been used widely to treat cerebral consequences of subarachnoid hemorrhage. It is known to have a positive effect on animal models of neurological disorders including Parkinson's disease and stroke. However, its cellular effect on progenitor populations and differentiation is not clearly understood. While recent studies suggest that fasudil promotes the mobilization of neural stem cells (NSCs) from the subventricular zone in vivo and promotes the differentiation of the C17...
April 2018: Stem Cell Research
https://www.readbyqxmd.com/read/29154191/integrin-cd11b-mediates-%C3%AE-synuclein-induced-activation-of-nadph-oxidase-through-a-rho-dependent-pathway
#4
Liyan Hou, Xiuqi Bao, Caixia Zang, Hanyu Yang, Fuqiang Sun, Yuning Che, Xuefei Wu, Shao Li, Dan Zhang, Qingshan Wang
The activation of microglial NADPH oxidase (NOX2) induced by α-synuclein has been implicated in Parkinson's disease (PD) and other synucleinopathies. However, how α-synuclein activates NOX2 remains unclear. Previous study revealed that both toll-like receptor 2 (TLR2) and integrin play important roles in α-synuclein-induced microglial activation. In this study, we found that blocking CD11b, the α chain of integrin αM β2 , but not TLR2 attenuated α-synuclein-induced NOX2 activation in microglia. The involvement of CD11b in α-synuclein-induced activation of NOX2 was further confirmed in CD11b-/- microglia by showing reduced membrane translocation of NOX2 cytosolic subunit p47phox and superoxide production...
April 2018: Redox Biology
https://www.readbyqxmd.com/read/28899515/the-water-extract-of-liuwei-dihuang-possesses-multi-protective-properties-on-neurons-and-muscle-tissue-against-deficiency-of-survival-motor-neuron-protein
#5
Yu-Ting Tseng, Yuh-Jyh Jong, Wei-Fang Liang, Fang-Rong Chang, Yi-Ching Lo
BACKGROUND: Deficiency of survival motor neuron (SMN) protein, which is encoded by the SMN1 and SMN2 genes, induces widespread splicing defects mainly in spinal motor neurons, and leads to spinal muscular atrophy (SMA). Currently, there is no effective treatment for SMA. Liuwei dihuang (LWDH), a traditional Chinese herbal formula, possesses multiple therapeutic benefits against various diseases via modulation of the nervous, immune and endocrine systems. Previously, we demonstrated water extract of LWDH (LWDH-WE) protects dopaminergic neurons and improves motor activity in models of Parkinson's disease...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28842414/the-atypical-map-kinase-swip-13-erk8-regulates-dopamine-transporters-through-a-rho-dependent-mechanism
#6
Daniel P Bermingham, J Andrew Hardaway, Osama Refai, Christian R Marks, Sam L Snider, Sarah M Sturgeon, William C Spencer, Roger J Colbran, David M Miller, Randy D Blakely
The neurotransmitter dopamine (DA) regulates multiple behaviors across phylogeny, with disrupted DA signaling in humans associated with addiction, attention-deficit/ hyperactivity disorder, schizophrenia, and Parkinson's disease. The DA transporter (DAT) imposes spatial and temporal limits on DA action, and provides for presynaptic DA recycling to replenish neurotransmitter pools. Molecular mechanisms that regulate DAT expression, trafficking, and function, particularly in vivo , remain poorly understood, though recent studies have implicated rho-linked pathways in psychostimulant action...
September 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28618343/design-synthesis-immunocytochemistry-evaluation-and-molecular-docking-investigation-of-several-4-aminopyridine-derivatives-as-potential-neuroprotective-agents-for-treating-parkinson-s-disease
#7
Shulin Li, Daiyan Wei, Zhuo Mao, Ligong Chen, Xilong Yan, Yang Li, Shengjie Dong, Donghua Wang
Neuroprotection refers to the relative preservation of neuronal structure and function. Neuroprotective agents refer to substances that are capable of preserving brain function and structure. Currently, there are no neuroprotective agents available that can effectively relieve the progression of Parkinson's disease. In this work, five novel 4-aminopyridine derivatives, including three amides and two ureas, were designed, synthesized, and evaluated using the rat PC12 mice pheochromocytoma cell line as an in vitro model...
August 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28484287/mir-135b-plays-a-neuroprotective-role-by-targeting-gsk3%C3%AE-in-mpp-intoxicated-sh-sy5y-cells
#8
Jianlei Zhang, Wei Liu, Yabo Wang, Shengnan Zhao, Na Chang
miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson's disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3 β (GSK3 β ) was upregulated at mRNA and protein levels in MPP+ -intoxicated SH-SY5Y cells in a dose- and time-dependent manner...
2017: Disease Markers
https://www.readbyqxmd.com/read/28420986/modulation-of-microglial-activity-by-rho-kinase-rock-inhibition-as-therapeutic-strategy-in-parkinson-s-disease-and-amyotrophic-lateral-sclerosis
#9
REVIEW
Anna-Elisa Roser, Lars Tönges, Paul Lingor
Neurodegenerative diseases are characterized by the progressive degeneration of neurons in the central and peripheral nervous system (CNS, PNS), resulting in a reduced innervation of target structures and a loss of function. A shared characteristic of many neurodegenerative diseases is the infiltration of microglial cells into affected brain regions. During early disease stages microglial cells often display a rather neuroprotective phenotype, but switch to a more pro-inflammatory neurotoxic phenotype in later stages of the disease, contributing to the neurodegeneration...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#10
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
February 2017: Neurochemical Research
https://www.readbyqxmd.com/read/27772760/role-of-rho-mediated-rock-semaphorin3a-signaling-pathway-in-the-pathogenesis-of-parkinson-s-disease-in-a-mouse-model
#11
Li Qi, Yong-Gang Tang, Lin Wang, Wei He, Hong-Hua Pan, Rong-Rong Nie, Yan Can
OBJECTIVE: The present study aims to elucidate the role of Rho-mediated ROCK-Semaphorin3A signaling pathway in the pathogenesis of Parkinson's disease (PD) in a mouse model. METHODS: One-hundred twelve eight-week male C57BL/6 mice were selected. The mouse model of PD was constructed by intraperitoneal injection of MPTP. All mice were divided into four groups (28 mice in each group): Blank group, Model group, Rho knockout (Rho+/-) group and ROCK knockout (ROCK+/-) group...
November 15, 2016: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/27541019/the-rock-ggtase-pathway-are-essential-to-the-proliferation-and-differentiation-of-neural-stem-cells-mediated-by-simvastatin
#12
Chan Zhang, Jian-Min Wu, Min Liao, Jun-Ling Wang, Chao-Jin Xu
Simvastatin, a lipophilic and fermentation-derived natural statin, is reported to treat neurological disorders, such as traumatic brain injury, Parkinson's disease (PD), Alzheimer disease (AD), etc. Recently, research also indicated that simvastatin could promote regeneration in the dentate gyrus of adult mice by Wnt/β-catenin signaling (Robin et al. in Stem Cell Reports 2:9-17, 2014). However, the effect and mechanisms by which simvastatin may affect the neural stem cells (NSCs; from the embryonic day 14...
December 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27234991/erratum-to-behavioural-effects-of-basal-ganglia-rho-kinase-inhibition-in-the-unilateral-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#13
Salim Yalcin Inan, Burak Cem Soner, Ayse Saide Sahin
No abstract text is available yet for this article.
August 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/27101974/fasudil-attenuates-aggregation-of-%C3%AE-synuclein-in-models-of-parkinson-s-disease
#14
Lars Tatenhorst, Katrin Eckermann, Vivian Dambeck, Luis Fonseca-Ornelas, Hagen Walle, Tomás Lopes da Fonseca, Jan C Koch, Stefan Becker, Lars Tönges, Mathias Bähr, Tiago F Outeiro, Markus Zweckstetter, Paul Lingor
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, yet disease-modifying treatments do not currently exist. Rho-associated protein kinase (ROCK) was recently described as a novel neuroprotective target in PD. Since alpha-synuclein (α-Syn) aggregation is a major hallmark in the pathogenesis of PD, we aimed to evaluate the anti-aggregative potential of pharmacological ROCK inhibition using the isoquinoline derivative Fasudil, a small molecule inhibitor already approved for clinical use in humans...
April 22, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27075764/effects-of-rho-kinase-inhibitors-on-grafts-of-dopaminergic-cell-precursors-in-a-rat-model-of-parkinson-s-disease
#15
Jannette Rodriguez-Pallares, Ana I Rodriguez-Perez, Ana Muñoz, Juan A Parga, Juan J Toledo-Aral, Jose L Labandeira-Garcia
UNLABELLED: In models of Parkinson's disease (PD), Rho kinase (ROCK) inhibitors have antiapoptotic and axon-stabilizing effects on damaged neurons, decrease the neuroinflammatory response, and protect against dopaminergic neuron death and axonal retraction. ROCK inhibitors have also shown protective effects against apoptosis induced by handling and dissociation of several types of stem cells. However, the effect of ROCK inhibitors on dopaminergic cell grafts has not been investigated...
June 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27033194/rock-in-cns-different-roles-of-isoforms-and-therapeutic-target-for-neurodegenerative-disorders
#16
REVIEW
Cheong-Meng Chong, Nana Ai, Simon Ming-Yuen Lee
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...
2017: Current Drug Targets
https://www.readbyqxmd.com/read/26996632/behavioural-effects-of-basal-ganglia-rho-kinase-inhibition-in-the-unilateral-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#17
Salim Yalcin Inan, Burak Cem Soner, Ayse Saide Sahin
Parkinson's disease (PD) is one of the most common neurodegenerative disorders, which affects more than six million people in the world. While current available pharmacological therapies for PD in the early stages of the disease usually improve motor symptoms, they cause side effects, such as fluctuations and dyskinesias in the later stages. In this later stage, high frequency deep brain stimulation of the subthalamic nucleus (STN-DBS) is a treatment option which is most successful to treat drug resistant advanced PD...
August 2016: Metabolic Brain Disease
https://www.readbyqxmd.com/read/26683082/fasudil-a-rho-kinase-inhibitor-promotes-the-autophagic-degradation-of-a53t-%C3%AE-synuclein-by-activating-the-jnk-1-bcl-2-beclin-1-pathway
#18
Feng-Tao Liu, Yu-Jie Yang, Jian-Jun Wu, Shan Li, Yi-Lin Tang, Jue Zhao, Zhen-Yang Liu, Bao-Guo Xiao, Ji Zuo, Wen Liu, Jian Wang
Accumulation of α-synuclein (α-syn) is pivotally implicated in the pathogenesis of Parkinson׳s disease (PD), and enhancing its clearance might be a promising strategy in PD treatment. It has recently been shown that Rho kinase (ROCK) activation is involved in many neurodegenerative diseases, and some ROCK inhibitors might promote the degradation of abnormal protein aggregates. However, it is not known if fasudil, the only ROCK inhibitor available in clinical setting, could promote the degradation of α-syn, and ameliorate the α-syn induced neurotoxicity...
February 1, 2016: Brain Research
https://www.readbyqxmd.com/read/26526034/csf-nrf2-and-hspa8-in-parkinson-s-disease-patients-with-and-without-lrrk2-gene-mutations
#19
David A Loeffler, Lynnae M Smith, Mary P Coffey, Jan O Aasly, Peter A LeWitt
Leucine-rich repeat kinase 2 (LRRK2) gene mutations are the most common genetic cause of Parkinson's disease (PD). CSF specimens from LRRK2 + PD patients and healthy LRRK2 mutation carriers are, therefore, useful for biomarker studies. This study examined the hypothesis that differences are present between subjects with sporadic PD (sPD), PD carriers of LRRK2 mutations (LRRK2 + PD), healthy control subjects lacking LRRK2 mutations (CTL), and LRRK2 mutation-carrying healthy controls (LRRK2 + CTL) for CSF concentrations of six potential PD biomarkers...
March 2016: Journal of Neural Transmission
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