{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:21:43Z","timestamp":1793726503882,"version":"4.6.1"},"reference-count":178,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T00:00:00Z","timestamp":1731974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009009","name":"Heilongjiang University of Chinese Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Neurodegenerative diseases (NDDs) are prevalent in the elderly. The pathogenesis of NDDs is complex, and currently, there is no cure available. With the increase in aging population, over 20 million people are affected by common NDDs alone (Alzheimer\u2019s disease and Parkinson\u2019s disease). Therefore, NDDs have profound negative impacts on patients, their families, and society, making them a major global health concern. Rho-associated kinases (ROCKs) belong to the serine\/threonine protein kinases family, which modulate diverse cellular processes (e.g., apoptosis). ROCKs may elevate the risk of various NDDs (including Huntington\u2019s disease, Parkinson\u2019s disease, and Alzheimer\u2019s disease) by disrupting synaptic plasticity and promoting inflammatory responses. Therefore, ROCK inhibitors have been regarded as ideal therapies for NDDs in recent years. Fasudil, one of the classic ROCK inhibitor, is a potential drug for treating NDDs, as it repairs nerve damage and promotes axonal regeneration. Thus, the current review summarizes the relationship between ROCKs and NDDs and the mechanism by which fasudil inhibits ROCKs to provide new ideas for the treatment of NDDs.<\/jats:p>","DOI":"10.3389\/fnins.2024.1481983","type":"journal-article","created":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T12:22:18Z","timestamp":1732018938000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Role of Rho-associated kinases and their inhibitor fasudil in neurodegenerative diseases"],"prefix":"10.3389","volume":"18","author":[{"given":"Qiuyan","family":"Ye","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayue","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengge","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1186\/1471-2407-14-412","article-title":"The rho-kinase inhibitor HA-1077 suppresses proliferation\/migration and induces apoptosis of urothelial cancer cells","volume":"2014","author":"Abe","year":"2014","journal-title":"BMC Cancer"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"3927","DOI":"10.1007\/s12035-015-9303-2","article-title":"Role of rho kinase inhibition in the protective effect of Fasudil and simvastatin against 3-Nitropropionic acid-induced striatal neurodegeneration and mitochondrial dysfunction in rats","volume":"53","author":"Ahmed","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1046\/j.1471-4159.2003.02054.x","article-title":"Identification of tau and MAP2 as novel substrates of rho-kinase and myosin phosphatase","volume":"87","author":"Amano","year":"2003","journal-title":"J. Neurochem."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1002\/cm.20472","article-title":"Rho-kinase\/ROCK: A key regulator of the cytoskeleton and cell polarity","volume":"67","author":"Amano","year":"2010","journal-title":"Cytoskeleton (Hoboken)."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"4639","DOI":"10.1007\/s12325-023-02550-w","article-title":"Phase 3 clinical trial comparing the safety and efficacy of Netarsudil to Ripasudil in patients with primary open-angle Glaucoma or ocular hypertension: Japan rho kinase elevated intraocular pressure treatment trial (J-ROCKET)","volume":"40","author":"Araie","year":"2023","journal-title":"Adv. Ther."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"241","DOI":"10.2174\/156720510791050902","article-title":"ADF\/Cofilin-actin rods in neurodegenerative diseases","volume":"7","author":"Bamburg","year":"2010","journal-title":"Curr. Alzheimer Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1038\/srep00809","article-title":"ROCK\/Cdc42-mediated microglial motility and gliapse formation lead to phagocytosis of degenerating dopaminergic neurons in vivo","volume":"2","author":"Barcia","year":"2012","journal-title":"Sci. Rep."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"13153","DOI":"10.1074\/jbc.M809229200","article-title":"Inhibition of rho kinases enhances the degradation of mutant huntingtin","volume":"284","author":"Bauer","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.3390\/cells9102279","article-title":"Rho family of Ras-like GTPases in early-branching animals","volume":"9","author":"Beljan","year":"2020","journal-title":"Cells"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/0022-510X(73)90175-5","article-title":"Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations","volume":"20","author":"Bernheimer","year":"1973","journal-title":"J. Neurol. Sci."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"8325","DOI":"10.1021\/bi027348m","article-title":"Inhibition of tau polymerization by its carboxy-terminal caspase cleavage fragment","volume":"42","author":"Berry","year":"2003","journal-title":"Biochemistry"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1007\/s40265-021-01593-z","article-title":"Belumosudil: First Approval","volume":"81","author":"Blair","year":"2021","journal-title":"Drugs"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"2776","DOI":"10.1523\/JNEUROSCI.0462-19.2020","article-title":"ROCK\/PKA inhibition rescues hippocampal Hyperexcitability and GABAergic neuron alterations in a Oligophrenin-1 Knock-out mouse model of X-linked intellectual disability","volume":"40","author":"Busti","year":"2020","journal-title":"J. Neurosci."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"113481","DOI":"10.1016\/j.bbr.2021.113481","article-title":"Role of RhoA\/ROCK signaling in Alzheimer\u2019s disease","volume":"414","author":"Cai","year":"2021","journal-title":"Behav. Brain Res."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"101446","DOI":"10.1016\/j.redox.2020.101446","article-title":"Distinct dual roles of p-Tyr42 RhoA GTPase in tau phosphorylation and ATP citrate lyase activation upon different A\u03b2 concentrations","volume":"32","author":"Cap","year":"2020","journal-title":"Redox Biol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1037\/a0023167","article-title":"ROCK inhibition prevents tau hyperphosphorylation and p25\/CDK5 increase after global cerebral ischemia","volume":"125","author":"Castro-Alvarez","year":"2011","journal-title":"Behav. Neurosci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"597","DOI":"10.3390\/antiox9070597","article-title":"The role of oxidative stress in Parkinson\u2019s disease","volume":"9","author":"Chang","year":"2020","journal-title":"Antioxidants (Basel)."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"12218","DOI":"10.1073\/pnas.0502698102","article-title":"Unraveling a role for dopamine in Huntington\u2019s disease: the dual role of reactive oxygen species and D2 receptor stimulation","volume":"102","author":"Charvin","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1038\/35000219","article-title":"Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1","volume":"403","author":"Chen","year":"2000","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1523\/JNEUROSCI.0089-14.2015","article-title":"A53T human \u03b1-synuclein overexpression in transgenic mice induces pervasive mitochondria macroautophagy defects preceding dopamine neuron degeneration","volume":"35","author":"Chen","year":"2015","journal-title":"J. Neurosci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1007\/s12017-015-8374-6","article-title":"Role of rho kinase and Fasudil on synaptic plasticity in multiple sclerosis","volume":"17","author":"Chen","year":"2015","journal-title":"NeuroMolecular Med."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1038\/mp.2016.214","article-title":"Caspase-3-dependent cleavage of Akt modulates tau phosphorylation via GSK3\u03b2 kinase: implications for Alzheimer\u2019s disease","volume":"22","author":"Chu","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"3919","DOI":"10.1074\/jbc.M111.301911","article-title":"Cofilin aggregation blocks intracellular trafficking and induces synaptic loss in hippocampal neurons","volume":"287","author":"Cichon","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1323563","DOI":"10.3389\/fnagi.2024.1323563","article-title":"Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer\u2019s disease","volume":"16","author":"Collu","year":"2024","journal-title":"Front. Aging Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.bbadis.2013.10.013","article-title":"Increased expression of myosin binding protein H in the skeletal muscle of amyotrophic lateral sclerosis patients","volume":"1842","author":"Conti","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3390\/cells10020401","article-title":"Rho GTPase signaling in health and disease: A complex signaling network","volume":"10","author":"Cord","year":"2021","journal-title":"Cells"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.jmgm.2013.09.009","article-title":"Associations between the rho kinase-1 catalytic and PH domain regulatory unit","volume":"2013","author":"Craft","year":"2013","journal-title":"J. Mol. Graph. Model."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"78764","DOI":"10.18632\/oncotarget.12853","article-title":"Fasudil, an inhibitor of rho-associated coiled-coil kinase, improves cognitive impairments induced by smoke exposure","volume":"7","author":"Deng","year":"2016","journal-title":"Oncotarget"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1111\/j.1365-2990.2007.00850.x","article-title":"Vascular endothelial growth factor counteracts the loss of phospho-Akt preceding motor neurone degeneration in amyotrophic lateral sclerosis","volume":"33","author":"Dewil","year":"2007","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e8287","DOI":"10.1371\/journal.pone.0008287","article-title":"Dopamine D2 receptor stimulation potentiates PolyQ-huntingtin-induced mouse striatal neuron dysfunctions via rho\/ROCK-II activation","volume":"4","author":"Deyts","year":"2009","journal-title":"PLoS One"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"135880","DOI":"10.1016\/j.neulet.2021.135880","article-title":"Fasudil enhances the phagocytosis of myelin debris and the expression of neurotrophic factors in cuprizone-induced demyelinating mice","volume":"753","author":"Ding","year":"2021","journal-title":"Neurosci. Lett."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1001\/jamaneurol.2017.3299","article-title":"The Parkinson pandemic-A call to action","volume":"75","author":"Dorsey","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The emerging evidence of the Parkinson pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Parkinsons Dis."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3874","DOI":"10.1016\/j.cub.2019.09.040","article-title":"RhoA controls axon extension independent of specification in the developing brain","volume":"29","author":"Dupraz","year":"2019","journal-title":"Curr. Biol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41398-018-0231-6","article-title":"A role for APP in Wnt signalling links synapse loss with \u03b2-amyloid production","volume":"8","author":"Elliott","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"eaav6221","DOI":"10.1126\/scitranslmed.aav6221","article-title":"Alzheimer\u2019s Disease Neuroimaging Initiative. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer\u2019s disease","volume":"11","author":"Ewers","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"14410","DOI":"10.3390\/ijms241914410","article-title":"Selective ROCK inhibitor enhances blood flow recovery after Hindlimb ischemia","volume":"24","author":"Fayed","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1093\/gbe\/evx100","article-title":"The evolutionary landscape of Dbl-like RhoGEF families: adapting eukaryotic cells to environmental signals","volume":"9","author":"Fort","year":"2017","journal-title":"Genome Biol. Evol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"175450","DOI":"10.1016\/j.ejphar.2022.175450","article-title":"The anti-asthmatic potential of rho-kinase inhibitor hydroxyfasudil in the model of experimentally induced allergic airway inflammation","volume":"938","author":"Franova","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"10032","DOI":"10.1073\/pnas.1630428100","article-title":"Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer\u2019s disease","volume":"100","author":"Gamblin","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1007\/s11011-019-00487-0","article-title":"The rho kinase inhibitor fasudil attenuates A\u03b21-42-induced apoptosis via the ASK1\/JNK signal pathway in primary cultures of hippocampal neurons","volume":"34","author":"Gao","year":"2019","journal-title":"Metab. Brain Dis."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e00362","DOI":"10.1002\/brb3.362","article-title":"An update on immunopathogenesis, diagnosis, and treatment of multiple sclerosis","volume":"5","author":"Garg","year":"2015","journal-title":"Brain Behav."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.3390\/biomedicines12051074","article-title":"Insights into Calpain activation and rho-ROCK signaling in Parkinson\u2019s disease and aging","volume":"12","author":"Gathings","year":"2024","journal-title":"Biomedicine"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1523\/JNEUROSCI.2336-15.2016","article-title":"Rho kinase inhibition as a therapeutic for progressive Supranuclear palsy and Corticobasal degeneration","volume":"36","author":"Gentry","year":"2016","journal-title":"J. Neurosci."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.3233\/JAD-230551","article-title":"Reduction of phosphorylated tau in Alzheimer\u2019s disease induced pluripotent stem cell-derived neuro-spheroids by rho-associated coiled-coil kinase inhibitor Fasudil","volume":"96","author":"Giunti","year":"2023","journal-title":"J. Alzheimers Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3946320241282949","DOI":"10.1177\/03946320241282949","article-title":"Anti-astmatic effect of ROCK inhibitor, GSK429286 A, in experimentally induced allergic airway inflammation","volume":"38","author":"Gond\u00e1\u0161","year":"2024","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3389\/fphar.2017.00017","article-title":"Rho kinase inhibition with Fasudil in the SOD1G93A mouse model of amyotrophic lateral sclerosis-symptomatic treatment potential after disease onset","volume":"8","author":"G\u00fcnther","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"577284","DOI":"10.1016\/j.jneuroim.2020.577284","article-title":"Fasudil inhibits the activation of microglia and astrocytes of transgenic Alzheimer\u2019s disease mice via the downregulation of TLR4\/Myd88\/NF-\u03baB pathway","volume":"346","author":"Guo","year":"","journal-title":"J. Neuroimmunol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"651","DOI":"10.31083\/j.jin.2020.04.243","article-title":"Fasudil reduces \u03b2-amyloid levels and neuronal apoptosis in APP\/PS1 transgenic mice via inhibition of the Nogo-A\/NgR\/RhoA signaling axis","volume":"19","author":"Guo","year":"","journal-title":"J. Integr. Neurosci."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1008","DOI":"10.3389\/fphar.2019.01008","article-title":"Neuroinflammation as a common feature of neurodegenerative disorders","volume":"10","author":"Guzman-Martinez","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e470","DOI":"10.1111\/aos.14949","article-title":"Sovesudil (locally acting rho kinase inhibitor) for the treatment of normal-tension glaucoma: the randomized phase II study","volume":"100","author":"Ha","year":"2022","journal-title":"Acta Ophthalmol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1007\/s00018-009-0189-x","article-title":"Rho-kinase inhibitors as therapeutics: from pan inhibition to isoform selectivity","volume":"67","author":"Hahmann","year":"2010","journal-title":"Cell. Mol. Life Sci."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.neurobiolaging.2019.12.009","article-title":"Rho-kinase ROCK inhibitors reduce oligomeric tau protein","volume":"89","author":"Hamano","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"17071","DOI":"10.1038\/nrdp.2017.71","article-title":"Amyotrophic lateral sclerosis","volume":"3","author":"Hardiman","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"119","DOI":"10.3892\/mmr.2017.6615","article-title":"Effect of fasudil on cognitive function following status convulsion in rats","volume":"16","author":"He","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1111\/jnc.13688","article-title":"Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer\u2019s disease and ROCK1 depletion reduces amyloid-\u03b2 levels in brain","volume":"138","author":"Henderson","year":"2016","journal-title":"J. Neurochem."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"eaaw9318","DOI":"10.1126\/scisignal.aaw9318","article-title":"Pharmacologic inhibition of LIMK1 provides dendritic spine resilience against \u03b2-amyloid","volume":"12","author":"Henderson","year":"2019","journal-title":"Sci. Signal."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"19086","DOI":"10.1523\/JNEUROSCI.2508-13.2013","article-title":"Pharmacologic inhibition of ROCK2 suppresses amyloid-\u03b2 production in an Alzheimer\u2019s disease mouse model","volume":"33","author":"Herskowitz","year":"2013","journal-title":"J. Neurosci."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.expneurol.2009.11.019","article-title":"Neurodegeneration in autoimmune CNS inflammation","volume":"225","author":"Herz","year":"2010","journal-title":"Exp Neurol. Sep"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1111\/j.1471-4159.2007.05194.x","article-title":"The GSK3 hypothesis of Alzheimer\u2019s disease","volume":"104","author":"Hooper","year":"2008","journal-title":"J. Neurochem."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"8759","DOI":"10.1007\/s12035-024-04138-z","article-title":"Oligomeric amyloid-\u03b2 and tau Alter cell adhesion properties and induce inflammatory responses in cerebral endothelial cells through the RhoA\/ROCK pathway","volume":"61","author":"Hossen","year":"","journal-title":"Mol. Neurobiol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.freeradbiomed.2024.05.044","article-title":"Oligomeric tau-induced oxidative damage and functional alterations in cerebral endothelial cells: role of RhoA\/ROCK signaling pathway","volume":"221","author":"Hossen","year":"","journal-title":"Free Radic. Biol. Med."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e13001","DOI":"10.1111\/acel.13001","article-title":"Rho-associated coiled-coil kinase 1 activation mediates amyloid precursor protein site-specific Ser655 phosphorylation and triggers amyloid pathology","volume":"18","author":"Hu","year":"2019","journal-title":"Aging Cell"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1186.e9","DOI":"10.1016\/j.urology.2011.12.032","article-title":"Hydroxyfasudil ameliorates bladder dysfunction in male spontaneously hypertensive rats","volume":"79","author":"Inoue","year":"2012","journal-title":"Urology"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"173815","DOI":"10.1016\/j.ejphar.2020.173815","article-title":"Role of RhoA-ROCK signaling in Parkinson\u2019s disease","volume":"894","author":"Iyer","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"3176","DOI":"10.1016\/j.neurobiolaging.2015.08.019","article-title":"Silencing of TREM2 exacerbates tau pathology, neurodegenerative changes, and spatial learning deficits in P301S tau transgenic mice","volume":"36","author":"Jiang","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"284","DOI":"10.13418\/j.issn.1001-165x.2024.3.08","article-title":"Fasudil promotes axon and myelin regeneration and functional recovery after sciatic nerve injury in rats","volume":"42","author":"Jing","year":"2024","journal-title":"Chinese journal of Clin. Anat."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.1002\/cne.24679","article-title":"ROCK inhibition improves axonal regeneration in a preclinical model of amyotrophic lateral sclerosis","volume":"527","author":"Joshi","year":"2019","journal-title":"J. Comp. Neurol."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"e29846","DOI":"10.4161\/sgtp.29846","article-title":"Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions","volume":"5","author":"Julian","year":"2014","journal-title":"Small GTPases."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"105028","DOI":"10.1016\/j.nbd.2020.105028","article-title":"Microglia and astrocyte dysfunction in Parkinson\u2019s disease","volume":"144","author":"Kam","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"19640","DOI":"10.1038\/srep19640","article-title":"Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm\u2019s canal endothelial cells","volume":"6","author":"Kaneko","year":"2016","journal-title":"Sci. Rep."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"11219","DOI":"10.3390\/ijms241311219","article-title":"Neurodegenerative disease associated pathways in the brains of triple transgenic Alzheimer\u2019s model mice are reversed following two weeks of peripheral Administration of Fasudil","volume":"24","author":"Killick","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3389\/fneur.2020.00173","article-title":"Compassionate use of the ROCK inhibitor Fasudil in three patients with amyotrophic lateral sclerosis","volume":"11","author":"Koch","year":"2020","journal-title":"Front. Neurol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2018.03.008","article-title":"ROCK inhibition in models of neurodegeneration and its potential for clinical translation","volume":"189","author":"Koch","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/lt.24020","article-title":"Rho-kinase inhibitor targeting the liver prevents ischemia\/reperfusion injury in the steatotic liver without major systemic adversity in rats","volume":"21","author":"Kuroda","year":"2015","journal-title":"Liver Transpl."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1523\/JNEUROSCI.3501-06.2007","article-title":"Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer\u2019s disease","volume":"27","author":"Lacor","year":"2007","journal-title":"J. Neurosci."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/1750-1326-6-39","article-title":"Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice","volume":"6","author":"Lasagna-Reeves","year":"2011","journal-title":"Mol. Neurodegener."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"446","DOI":"10.3390\/biomedicines10020446","article-title":"Inflammation and rho-associated protein kinase-induced brain changes in vascular dementia","volume":"10","author":"Lee","year":"2022","journal-title":"Biomedicine"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1002\/jcp.28965","article-title":"RKI-1447 suppresses colorectal carcinoma cell growth via disrupting cellular bioenergetics and mitochondrial dynamics","volume":"235","author":"Li","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"41227","DOI":"10.1038\/srep41227","article-title":"FSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms","volume":"7","author":"Li","year":"2017","journal-title":"Sci. Rep."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"e56026","DOI":"10.1371\/journal.pone.0056026","article-title":"Intravitreal administration of HA-1077, a ROCK inhibitor, improves retinal function in a mouse model of Huntington disease","volume":"8","author":"Li","year":"2013","journal-title":"PLoS One"},{"key":"ref83","doi-asserted-by":"publisher","first-page":"29","DOI":"10.16557\/j.cnki.1000-7547.2020.01.005","article-title":"The expression of RhoA and ROCK2 in the spinal cord of SOD1-G93A transgenic mice","volume":"36","author":"Liang","year":"2020","journal-title":"Chinese J. Neuroanatomy."},{"key":"ref84","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.neuroscience.2010.05.020","article-title":"Accelerated neurite growth from spiral ganglion neurons exposed to the rho kinase inhibitor H-1152","volume":"169","author":"Lie","year":"2010","journal-title":"Neuroscience"},{"key":"ref85","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/j.bbadis.2012.04.007","article-title":"Role of hippocalcin in mediating A\u03b2 toxicity","volume":"1822","author":"Lim","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/j.1471-4159.2007.04756.x","article-title":"Inhibition of rho kinase (ROCK) increases neurite outgrowth on chondroitin sulphate proteoglycan in vitro and axonal regeneration in the adult optic nerve in vivo","volume":"103","author":"Lingor","year":"2007","journal-title":"J. Neurochem."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"671","DOI":"10.4103\/1673-5374.379050","article-title":"Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis","volume":"19","author":"Liu","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.brainres.2015.12.002","article-title":"Fasudil, a rho kinase inhibitor, promotes the autophagic degradation of A53T \u03b1-synuclein by activating the JNK 1\/Bcl-2\/beclin 1 pathway","volume":"1632","author":"Liu","year":"2016","journal-title":"Brain Res."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"5622","DOI":"10.1111\/bph.15275","article-title":"Rho kinase inhibitor fasudil reduces l-DOPA-induced dyskinesia in a rat model of Parkinson\u2019s disease","volume":"177","author":"Lopez-Lopez","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jneuroim.2018.02.001","article-title":"The inhibition of CB1 receptor accelerates the onset and development of EAE possibly by regulating microglia\/macrophages polarization","volume":"317","author":"Lou","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"104871","DOI":"10.1016\/j.neubiorev.2022.104871","article-title":"ROCK2 inhibition: A futuristic approach for the management of Alzheimer\u2019s disease","volume":"142","author":"Mani","year":"2022","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s10654-018-0392-x","article-title":"Age-specific ALS incidence: a dose-response meta-analysis","volume":"33","author":"Marin","year":"2018","journal-title":"Eur. J. Epidemiol."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"113742","DOI":"10.1016\/j.ejmech.2021.113742","article-title":"Emerging targets in drug discovery against neurodegenerative diseases: control of synapsis disfunction by the RhoA\/ROCK pathway","volume":"225","author":"Mart\u00edn-C\u00e1mara","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1002\/j.1460-2075.1996.tb00574.x","article-title":"Rho-associated kinase, a novel serine\/threonine kinase, as a putative target for small GTP binding protein rho","volume":"15","author":"Matsui","year":"1996","journal-title":"EMBO J."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1111\/ene.13413","article-title":"Huntington\u2019s disease: a clinical review","volume":"25","author":"McColgan","year":"2018","journal-title":"Eur. J. Neurol."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1111\/j.1471-4159.2009.06511.x","article-title":"Tau oligomers and aggregation in Alzheimer\u2019s disease","volume":"112","author":"Meraz-R\u00edos","year":"2010","journal-title":"J. Neurochem."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1007\/s12035-013-8568-6","article-title":"Opposing signaling of ROCK1 and ROCK2 determines the switching of substrate specificity and the mode of migration of glioblastoma cells","volume":"49","author":"Mertsch","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1016\/j.drudis.2010.06.011","article-title":"Rho-kinase inhibition: a novel therapeutic target for the treatment of cardiovascular diseases","volume":"15","author":"Ming","year":"2010","journal-title":"Drug Discov. Today"},{"key":"ref99","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1097\/ICO.0000000000001823","article-title":"Topical rho-associated kinase inhibitor, Y27632, accelerates corneal endothelial regeneration in a canine cryoinjury model","volume":"38","author":"Miyagi","year":"2019","journal-title":"Cornea"},{"key":"ref100","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1146\/annurev.neuro.28.061604.135718","article-title":"Molecular pathophysiology of Parkinson\u2019s disease","volume":"28","author":"Moore","year":"2005","journal-title":"Annu. Rev. Neurosci."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S1474-4422(22)00027-8","article-title":"Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer\u2019s disease: a longitudinal observational study","volume":"21","author":"Morenas-Rodr\u00edguez","year":"2022","journal-title":"Lancet Neurol."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1086\/644537","article-title":"What is a pandemic?","volume":"200","author":"Morens","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41467-019-13781-3","article-title":"ROCK inhibitors upregulate the neuroprotective Parkin-mediated mitophagy pathway","volume":"11","author":"Moskal","year":"2020","journal-title":"Nat. Commun."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.neures.2010.12.009","article-title":"Loss of striatal dopaminergic terminals during the early stage in response to MPTP injection in C57BL\/6 mice","volume":"69","author":"Muroyama","year":"2011","journal-title":"Neurosci. Res."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.celrep.2014.01.044","article-title":"The Wnt\/planar cell polarity pathway component Vangl2 induces synapse formation through direct control of N-cadherin","volume":"6","author":"Nagaoka","year":"2014","journal-title":"Cell Rep."},{"key":"ref106","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0014-5793(96)00811-3","article-title":"ROCK-I and ROCK-II, two isoforms of rho-associated coiled-coil forming protein serine\/threonine kinase in mice","volume":"392","author":"Nakagawa","year":"1996","journal-title":"FEBS Lett."},{"key":"ref107","doi-asserted-by":"publisher","first-page":"2132","DOI":"10.1007\/s12035-015-9147-9","article-title":"Rho kinase pathway alterations in the brain and leukocytes in Huntington\u2019s disease","volume":"53","author":"Narayanan","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref108","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1083\/jcb.201504046","article-title":"ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity","volume":"210","author":"Newell-Litwa","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref109","doi-asserted-by":"publisher","first-page":"3577","DOI":"10.1074\/jbc.275.5.3577","article-title":"Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop","volume":"275","author":"Ohashi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref110","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1124\/mol.107.044230","article-title":"Inhibition of rho family functions by lovastatin promotes myelin repair in ameliorating experimental autoimmune encephalomyelitis","volume":"73","author":"Paintlia","year":"2008","journal-title":"Mol. Pharmacol."},{"key":"ref111","doi-asserted-by":"publisher","first-page":"5025","DOI":"10.1158\/0008-5472.CAN-12-0954","article-title":"RKI-1447 is a potent inhibitor of the rho-associated ROCK kinases with anti-invasive and antitumor activities in breast cancer","volume":"72","author":"Patel","year":"2012","journal-title":"Cancer Res."},{"key":"ref112","doi-asserted-by":"publisher","first-page":"1759091414538134","DOI":"10.1177\/1759091414538134","article-title":"Induction of oligodendrocyte differentiation and in vitro myelination by inhibition of rho-associated kinase","volume":"6","author":"Pedraza","year":"2014","journal-title":"ASN Neuro"},{"key":"ref113","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s00441-012-1432-6","article-title":"The role of Nogo-A in axonal plasticity, regrowth and repair","volume":"349","author":"Pernet","year":"2012","journal-title":"Cell Tissue Res."},{"key":"ref114","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1093\/brain\/awm260","article-title":"The beta-amyloid protein of Alzheimer\u2019s disease increases neuronal CRMP-2 phosphorylation by a rho-GTP mechanism","volume":"131","author":"Petratos","year":"2008","journal-title":"Brain"},{"key":"ref115","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.3892\/or.2017.5397","article-title":"Targeting ROCK2 rather than ROCK1 inhibits Ewing sarcoma malignancy","volume":"37","author":"Pinca","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref116","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/S0896-6273(03)00697-4","article-title":"A rapid cellular FRET assay of polyglutamine aggregation identifies a novel inhibitor","volume":"40","author":"Pollitt","year":"2003","journal-title":"Neuron"},{"key":"ref117","doi-asserted-by":"publisher","first-page":"1939","DOI":"10.1038\/ncomms2927","article-title":"Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic mice","volume":"4","author":"Pozueta","year":"2013","journal-title":"Nat. Commun."},{"key":"ref118","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jns.2016.08.061","article-title":"Role of rho-mediated ROCK-Semaphorin3A signaling pathway in the pathogenesis of Parkinson\u2019s disease in a mouse model","volume":"370","author":"Qi","year":"2016","journal-title":"J. Neurol. Sci."},{"key":"ref119","doi-asserted-by":"publisher","first-page":"e16973","DOI":"10.7759\/cureus.16973","article-title":"Role of rho-associated protein kinase inhibition as therapeutic strategy for Parkinson\u2019s disease: dopaminergic survival and enhanced Mitophagy","volume":"13","author":"Quadir","year":"2021","journal-title":"Cureus."},{"key":"ref120","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1895\/wormbook.1.67.2","article-title":"Small GTPases","volume":"2018","author":"Reiner","year":"2018","journal-title":"WormBook"},{"key":"ref121","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1161\/01.STR.0000181077.84981.11","article-title":"Inhibition of rho kinase (ROCK) leads to increased cerebral blood flow and stroke protection","volume":"36","author":"Rikitake","year":"2005","journal-title":"Stroke"},{"key":"ref122","doi-asserted-by":"publisher","first-page":"858069","DOI":"10.3389\/fimmu.2022.858069","article-title":"ROCK inhibition with Y-27632 reduces joint inflammation and damage in serum-induced arthritis model and decreases in vitro osteoclastogenesis in patients with early arthritis","volume":"2022","author":"Rodr\u00edguez-Trillo","year":"2022","journal-title":"Front. Immunol."},{"key":"ref123","doi-asserted-by":"publisher","first-page":"106847","DOI":"10.1016\/j.phrs.2023.106847","article-title":"Small molecule protein kinase inhibitors approved by regulatory agencies outside of the United States","volume":"194","author":"Roskoski","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref124","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.bbrc.2008.04.148","article-title":"ROCK, PAK, and toll of synapses in Alzheimer\u2019s disease","volume":"371","author":"Salminen","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref125","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1254\/jphs.11075FP","article-title":"Antivasospastic effects of hydroxyfasudil, a rho-kinase inhibitor, after subarachnoid hemorrhage","volume":"118","author":"Satoh","year":"2012","journal-title":"J. Pharmacol. Sci."},{"key":"ref126","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.3390\/cells11091520","article-title":"RhoA signaling in neurodegenerative diseases","volume":"11","author":"Schmidt","year":"2022","journal-title":"Cells"},{"key":"ref127","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1074\/jbc.RA119.009896","article-title":"A proteolytic C-terminal fragment of Nogo-A (reticulon-4A) is released in exosomes and potently inhibits axon regeneration","volume":"295","author":"Sekine","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref128","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.jalz.2017.09.008","article-title":"Amyloid \u03b2 synaptotoxicity is Wnt-PCP dependent and blocked by fasudil","volume":"14","author":"Sellers","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref129","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1111\/jsm.12613","article-title":"Hydroxyl fasudil, an inhibitor of rho signaling, improves erectile function in diabetic rats: a role for neuronal ROCK","volume":"11","author":"Sezen","year":"2014","journal-title":"J. Sex. Med."},{"key":"ref130","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.imlet.2019.12.012","article-title":"Targeting ROCK signaling in health, malignant and non-malignant diseases","volume":"219","author":"Shahbazi","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref131","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1016\/j.febslet.2008.04.009","article-title":"ROCK and PRK-2 mediate the inhibitory effect of Y-27632 on polyglutamine aggregation","volume":"582","author":"Shao","year":"","journal-title":"FEBS Lett."},{"key":"ref132","doi-asserted-by":"publisher","first-page":"5196","DOI":"10.1128\/MCB.00079-08","article-title":"Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation","volume":"28","author":"Shao","year":"","journal-title":"Mol. Cell. Biol."},{"key":"ref133","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.nbd.2018.12.015","article-title":"Rho-kinase inhibition has antidepressant-like efficacy and expedites dendritic spine pruning in adolescent mice","volume":"124","author":"Shapiro","year":"2019","journal-title":"Neurobiol. Dis."},{"key":"ref134","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1111\/jnc.14817","article-title":"Microglial ROCK is essential for chronic methylmercury-induced neurodegeneration","volume":"151","author":"Shinozaki","year":"2019","journal-title":"J. Neurochem."},{"key":"ref135","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1111\/cns.12116","article-title":"Rho kinase inhibitor fasudil protects against \u03b2-amyloid-induced hippocampal neurodegeneration in rats","volume":"19","author":"Song","year":"2013","journal-title":"CNS Neurosci. Ther."},{"key":"ref136","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1002\/dneu.22138","article-title":"Postsynaptic assembly: a role for Wnt signaling","volume":"74","author":"Stamatakou","year":"2014","journal-title":"Dev. Neurobiol."},{"key":"ref137","doi-asserted-by":"publisher","first-page":"104743","DOI":"10.1016\/j.nbd.2020.104743","article-title":"Dysregulation of Rac or rho elicits death of motor neurons and activation of these GTPases is altered in the G93A mutant hSOD1 mouse model of amyotrophic lateral sclerosis","volume":"136","author":"Stankiewicz","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref138","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1111\/bph.12277","article-title":"Fasudil, a rho kinase inhibitor, limits motor neuron loss in experimental models of amyotrophic lateral sclerosis","volume":"170","author":"Takata","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref139","doi-asserted-by":"publisher","first-page":"28554","DOI":"10.1074\/jbc.M109.006296","article-title":"Ca2+\/calmodulin-dependent protein kinase IV-mediated LIM kinase activation is critical for calcium signal-induced neurite outgrowth","volume":"284","author":"Takemura","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref140","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40478-016-0310-y","article-title":"Fasudil attenuates aggregation of \u03b1-synuclein in models of Parkinson\u2019s disease","volume":"4","author":"Tatenhorst","year":"2016","journal-title":"Acta Neuropathol. Commun."},{"key":"ref141","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1097\/NEN.0000000000000095","article-title":"Rho kinase inhibition by fasudil in the striatal 6-hydroxydopamine lesion mouse model of Parkinson disease","volume":"73","author":"Tatenhorst","year":"2014","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref142","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/S1474-4422(21)00170-8","article-title":"Multiple sclerosis under the spotlight","volume":"20","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref143","doi-asserted-by":"publisher","first-page":"16524","DOI":"10.1038\/srep16524","article-title":"Cofilin 1 activation prevents the defects in axon elongation and guidance induced by extracellular alpha-synuclein","volume":"5","author":"Tilve","year":"2015","journal-title":"Sci. Rep."},{"key":"ref144","doi-asserted-by":"publisher","first-page":"3355","DOI":"10.1093\/brain\/aws254","article-title":"Inhibition of rho kinase enhances survival of dopaminergic neurons and attenuates axonal loss in a mouse model of Parkinson\u2019s disease","volume":"135","author":"T\u00f6nges","year":"2012","journal-title":"Brain"},{"key":"ref145","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/glia.22601","article-title":"Rho kinase inhibition modulates microglia activation and improves survival in a model of amyotrophic lateral sclerosis","volume":"62","author":"T\u00f6nges","year":"2014","journal-title":"Glia"},{"key":"ref146","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.tcb.2012.08.001","article-title":"The nuclear factor kappa B signaling pathway: integrating metabolism with inflammation","volume":"22","author":"Tornatore","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref147","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1002\/ptr.6259","article-title":"The novel protective effects of loganin against 1-methyl-4-phenylpyridinium-induced neurotoxicity: enhancement of neurotrophic signaling, activation of IGF-1R\/GLP-1R, and inhibition of RhoA\/ROCK pathway","volume":"33","author":"Tseng","year":"2019","journal-title":"Phytother. Res."},{"key":"ref148","doi-asserted-by":"publisher","first-page":"2093","DOI":"10.1016\/j.febslet.2008.04.039","article-title":"Rho GTPases in cancer cell biology","volume":"582","author":"Vega","year":"2008","journal-title":"FEBS Lett."},{"key":"ref149","doi-asserted-by":"publisher","first-page":"890","DOI":"10.3390\/antiox10060890","article-title":"NADPH oxidases (NOX): an overview from discovery, molecular mechanisms to physiology and pathology","volume":"10","author":"Vermot","year":"2021","journal-title":"Antioxidants (Basel)."},{"key":"ref150","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1016\/j.jacc.2005.07.047","article-title":"Fasudil study group. Efficacy and safety of fasudil in patients with stable angina: a double-blind, placebo-controlled, phase 2 trial","volume":"46","author":"Vicari","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref151","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-1-4939-9124-2_1","article-title":"Assays for neuronal defects caused by early formation of \u03b1-Synuclein inclusions in primary cultured neurons","volume":"1948","author":"Volpicelli-Daley","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref152","doi-asserted-by":"publisher","first-page":"e919220","DOI":"10.12659\/MSM.919220","article-title":"The effects of RKI-1447 in a mouse model of nonalcoholic fatty liver disease induced by a high-fat diet and in HepG2 human hepatocellular carcinoma cells treated with oleic acid","volume":"26","author":"Wang","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref153","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.biopha.2017.01.069","article-title":"Y-27632, a rho-associated protein kinase inhibitor, inhibits systemic lupus erythematosus","volume":"88","author":"Wang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref154","doi-asserted-by":"publisher","first-page":"e13515","DOI":"10.1111\/acel.13515","article-title":"Nogo receptor impairs the clearance of fibril amyloid-\u03b2 by microglia and accelerates Alzheimer\u2019s-like disease progression","volume":"20","author":"Wang","year":"2021","journal-title":"Aging Cell"},{"key":"ref155","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.4103\/1673-5374.187018","article-title":"Lim kinase, a bi-functional effector in injury-induced structural plasticity of synapses","volume":"11","author":"Wang","year":"2016","journal-title":"Neural Regen. Res."},{"key":"ref156","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1161\/CIRCRESAHA.108.188524","article-title":"ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells","volume":"104","author":"Wang","year":"2009","journal-title":"Circ. Res."},{"key":"ref157","doi-asserted-by":"publisher","first-page":"32","DOI":"10.5114\/fn.2021.105130","article-title":"Fasudil ameliorates cognitive deficits, oxidative stress and neuronal apoptosis via inhibiting ROCK\/MAPK and activating Nrf2 signalling pathways in APP\/PS1 mice","volume":"59","author":"Wei","year":"2021","journal-title":"Folia Neuropathol."},{"key":"ref158","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1186\/1745-6215-15-284","article-title":"Improving well-being and health for people with dementia (WHELD): study protocol for a randomised controlled trial","volume":"15","author":"Whitaker","year":"2014","journal-title":"Trials"},{"key":"ref159","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1007\/s10571-012-9845-z","article-title":"Rho-kinase inhibitor, fasudil, prevents neuronal apoptosis via the Akt activation and PTEN inactivation in the ischemic penumbra of rat brain","volume":"32","author":"Wu","year":"2012","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref160","doi-asserted-by":"publisher","first-page":"7859","DOI":"10.3748\/wjg.v27.i45.7859","article-title":"Therapeutic potentials of fasudil in liver fibrosis","volume":"27","author":"Xi","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref161","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41531-022-00402-y","article-title":"Mitophagy and reactive oxygen species interplay in Parkinson\u2019s disease","volume":"8","author":"Xiao","year":"2022","journal-title":"NPJ Parkinsons Dis"},{"key":"ref162","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3892\/mmr.2011.692","article-title":"Nogo-66 receptor activation inhibits neurite outgrowth and increases \u03b2-amyloid protein secretion of cortical neurons","volume":"5","author":"Xiao","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref163","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1111\/cea.12606","article-title":"Rho-kinase inhibitor fasudil reduces allergic airway inflammation and mucus hypersecretion by regulating STAT6 and NF\u03baB","volume":"45","author":"Xie","year":"2015","journal-title":"Clin. Exp. Allergy"},{"key":"ref164","doi-asserted-by":"publisher","first-page":"25035","DOI":"10.18632\/aging.103970","article-title":"\u03b4-Opioid receptor activation protects against Parkinson\u2019s disease-related mitochondrial dysfunction by enhancing PINK1\/Parkin-dependent mitophagy","volume":"12","author":"Xu","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"ref165","doi-asserted-by":"publisher","first-page":"755164","DOI":"10.3389\/fnagi.2021.755164","article-title":"Inhibition of rho kinase by Fasudil ameliorates cognition impairment in APP\/PS1 transgenic mice via modulation of gut microbiota and metabolites","volume":"13","author":"Yan","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref166","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1007\/s12264-019-00351-2","article-title":"Comparative study of ROCK1 and ROCK2 in hippocampal spine formation and synaptic function","volume":"35","author":"Yan","year":"2019","journal-title":"Neurosci. Bull."},{"key":"ref167","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1146\/annurev-pathmechdis-031521-034145","article-title":"Genetics and pathogenesis of Parkinson\u2019s syndrome","volume":"18","author":"Ye","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"ref168","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1083\/jcb.200412043","article-title":"The rho kinases I and II regulate different aspects of myosin II activity","volume":"170","author":"Yoneda","year":"2005","journal-title":"J. Cell Biol."},{"key":"ref169","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1007\/s11011-021-00689-5","article-title":"Cellular and molecular pathophysiology in the progression of Parkinson\u2019s disease","volume":"36","author":"Zaman","year":"2021","journal-title":"Metab. Brain Dis."},{"key":"ref170","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s13041-021-00833-3","article-title":"Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP\/PS1 mice","volume":"14","author":"Zhang","year":"2021","journal-title":"Mol. Brain"},{"key":"ref171","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1186\/s12974-021-02334-5","article-title":"Mitophagy in neurological disorders","volume":"18","author":"Zhang","year":"2021","journal-title":"J. Neuroinflammation"},{"key":"ref172","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1159\/000351221","article-title":"Rho kinase inhibitor fasudil regulates microglia polarization and function","volume":"20","author":"Zhang","year":"2013","journal-title":"Neuroimmunomodulation"},{"key":"ref173","doi-asserted-by":"publisher","first-page":"6670","DOI":"10.1038\/s41467-023-42505-x","article-title":"Soluble TREM2 ameliorates tau phosphorylation and cognitive deficits through activating transgelin-2 in Alzheimer\u2019s disease","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref174","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1007\/s10571-019-00668-6","article-title":"Involvement of RhoA\/ROCK signaling in A\u03b2-induced chemotaxis, cytotoxicity and inflammatory response of microglial BV2 cells","volume":"39","author":"Zhang","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref175","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.jns.2015.03.022","article-title":"Multitarget intervention of Fasudil in the neuroprotection of dopaminergic neurons in MPTP-mouse model of Parkinson\u2019s disease","volume":"353","author":"Zhao","year":"2015","journal-title":"J. Neurol. Sci."},{"key":"ref176","doi-asserted-by":"publisher","first-page":"421","DOI":"10.2176\/nmc.46.421","article-title":"Effect of fasudil hydrochloride, a protein kinase inhibitor, on cerebral vasospasm and delayed cerebral ischemic symptoms after aneurysmal subarachnoid hemorrhage","volume":"46","author":"Zhao","year":"2006","journal-title":"Neurol. Med. Chir. (Tokyo)"},{"key":"ref177","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1177\/0964528420912248","article-title":"Manual acupuncture relieves microglia-mediated neuroinflammation in a rat model of traumatic brain injury by inhibiting the RhoA\/ROCK2 pathway","volume":"38","author":"Zhu","year":"2020","journal-title":"Acupunct. Med."},{"key":"ref178","doi-asserted-by":"publisher","first-page":"e13587","DOI":"10.1111\/acel.13587","article-title":"Acrolein, an endogenous aldehyde induces synaptic dysfunction in vitro and in vivo: involvement of RhoA\/ROCK2 pathway","volume":"21","author":"Zhu","year":"2022","journal-title":"Aging Cell"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2024.1481983\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T12:22:24Z","timestamp":1732018944000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2024.1481983\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,19]]},"references-count":178,"alternative-id":["10.3389\/fnins.2024.1481983"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2024.1481983","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,19]]},"article-number":"1481983"}}