{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T15:38:00Z","timestamp":1785598680741,"version":"3.56.0"},"reference-count":76,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M013944\/1"],"award-info":[{"award-number":["MR\/M013944\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The pan Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor fasudil acts as a vasodilator and has been used as a medication for post-cerebral stroke for the past 29 years in Japan and China. More recently, based on the involvement of ROCK inhibition in synaptic function, neuronal survival, and processes associated with neuroinflammation, it has been suggested that the drug may be repurposed for neurodegenerative diseases. Indeed, fasudil has demonstrated preclinical efficacy in many neurodegenerative disease models. To facilitate an understanding of the wider biological processes at play due to ROCK inhibition in the context of neurodegeneration, we performed a global gene expression analysis on the brains of Alzheimer\u2019s disease model mice treated with fasudil via peripheral IP injection. We then performed a comparative analysis of the fasudil-driven transcriptional profile with profiles generated from a meta-analysis of multiple neurodegenerative diseases. Our results show that fasudil tends to drive gene expression in a reverse sense to that seen in brains with post-mortem neurodegenerative disease. The results are most striking in terms of pathway enrichment analysis, where pathways perturbed in Alzheimer\u2019s and Parkinson\u2019s diseases are overwhelmingly driven in the opposite direction by fasudil treatment. Thus, our results bolster the repurposing potential of fasudil by demonstrating an anti-neurodegenerative phenotype in a disease context and highlight the potential of in vivo transcriptional profiling of drug activity.<\/jats:p>","DOI":"10.3390\/ijms241311219","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:35:21Z","timestamp":1688949321000},"page":"11219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"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"],"prefix":"10.3390","volume":"24","author":[{"given":"Richard","family":"Killick","sequence":"first","affiliation":[{"name":"Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, Denmark Hill, London SE5 8AF, UK"},{"name":"College of Medicine and Health, University of Exeter, Exeter EX1 2UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Elliott","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2854-2576","authenticated-orcid":false,"given":"Elena","family":"Ribe","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, Denmark Hill, London SE5 8AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Broadstock","sequence":"additional","affiliation":[{"name":"Wolfson CARD, King\u2019s College London, London Bridge, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive","family":"Ballard","sequence":"additional","affiliation":[{"name":"College of Medicine and Health, University of Exeter, Exeter EX1 2UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, Denmark Hill, London SE5 8AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9205-4943","authenticated-orcid":false,"given":"Gareth","family":"Williams","sequence":"additional","affiliation":[{"name":"Wolfson CARD, King\u2019s College London, London Bridge, London SE1 1UL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/s41582-020-0397-4","article-title":"Drug repositioning and repurposing for Alzheimer disease","volume":"16","author":"Ballard","year":"2020","journal-title":"Nat. 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