{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:43:05Z","timestamp":1783636985910,"version":"3.55.0"},"reference-count":188,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Mental Health","award":["1R01MH113986"],"award-info":[{"award-number":["1R01MH113986"]}]},{"name":"National Institutes of Mental Health","award":["R01NS118197"],"award-info":[{"award-number":["R01NS118197"]}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["1R01MH113986"],"award-info":[{"award-number":["1R01MH113986"]}]},{"name":"National Institute of Neurological Disorders and Stroke","award":["R01NS118197"],"award-info":[{"award-number":["R01NS118197"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Astrocytes, vital support cells in the central nervous system (CNS), are crucial for maintaining neuronal health. In neurodegenerative diseases such as Alzheimer\u2019s disease (AD), astrocytes play a key role in clearing toxic amyloid-\u03b2 (A\u03b2) peptides. A\u03b2, a potent neuroinflammatory trigger, stimulates astrocytes to release excessive glutamate and inflammatory factors, exacerbating neuronal dysfunction and death. Recent studies underscore the role of Rho GTPases\u2014particularly RhoA, Rac1, and Cdc42\u2014in regulating A\u03b2 clearance and neuroinflammation. These key regulators of cytoskeletal dynamics and intracellular signaling pathways function independently through distinct mechanisms but may converge to modulate inflammatory responses. Their influence on astrocyte structure and function extends to regulating endothelin-converting enzyme (ECE) activity, which modulates vasoactive peptides such as endothelin-1 (ET-1). Through these processes, Rho GTPases impact vascular permeability and neuroinflammation, contributing to AD pathogenesis by affecting both A\u03b2 clearance and cerebrovascular interactions. Understanding the interplay between Rho GTPases and the cerebrovascular system provides fresh insights into AD pathogenesis. Targeting Rho GTPase signaling pathways in astrocytes could offer a promising therapeutic approach to mitigate neuroinflammation, enhance A\u03b2 clearance, and slow disease progression, ultimately improving cognitive outcomes in AD patients.<\/jats:p>","DOI":"10.3390\/brainsci14121239","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T08:40:10Z","timestamp":1733820010000},"page":"1239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Clearing Amyloid-Beta by Astrocytes: The Role of Rho GTPases Signaling Pathways as Potential Therapeutic Targets"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-8813","authenticated-orcid":false,"given":"Gyeongah","family":"Park","sequence":"first","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0540-5173","authenticated-orcid":false,"given":"Zhen","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2336-2170","authenticated-orcid":false,"given":"Hui","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, School of Medicine, The George Washington University, Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4342-0975","authenticated-orcid":false,"given":"Jianyang","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","unstructured":"Wei, D.C., and Morrison, E.H. 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