Rock inhibitors in Alzheimer’s disease

Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and cause of dementia. AD pathology primarily involves the formation of amyloid β (Aβ) plaques and neurofibrillary tangles containing hyperphosphorylated tau (p-tau). While Aβ targeted treatments have shown clinical pr...

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Main Authors: Chao Zheng, Weiming Xia, Jianhua Zhang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Aging
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Online Access:https://www.frontiersin.org/articles/10.3389/fragi.2025.1547883/full
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author Chao Zheng
Chao Zheng
Weiming Xia
Weiming Xia
Weiming Xia
Jianhua Zhang
author_facet Chao Zheng
Chao Zheng
Weiming Xia
Weiming Xia
Weiming Xia
Jianhua Zhang
author_sort Chao Zheng
collection DOAJ
description Alzheimer’s disease (AD) is the most common age-related neurodegenerative disease and cause of dementia. AD pathology primarily involves the formation of amyloid β (Aβ) plaques and neurofibrillary tangles containing hyperphosphorylated tau (p-tau). While Aβ targeted treatments have shown clinical promise, other aspects of AD pathology such as microgliosis, astrocytosis, synaptic loss, and hypometabolism may be viable targets for treatment. Among notable novel therapeutic approaches, the Ras homolog (Rho)-associated kinases (ROCKs) are being investigated as targets for AD treatment, based on the observations that ROCK1/2 levels are elevated in AD, and activation or inhibition of ROCKs changes dendritic/synaptic structures, protein aggregate accumulation, inflammation, and gliosis. This review will highlight key findings on the effects of ROCK inhibition in Aβ and ptau pathologies, as well as its effects on neuroinflammation, synaptic density, and potentially metabolism and bioenergetics.
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issn 2673-6217
language English
publishDate 2025-03-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Aging
spelling doaj-art-3eeb91e26d8845e6995ce18c35c4de0e2025-08-20T02:50:45ZengFrontiers Media S.A.Frontiers in Aging2673-62172025-03-01610.3389/fragi.2025.15478831547883Rock inhibitors in Alzheimer’s diseaseChao Zheng0Chao Zheng1Weiming Xia2Weiming Xia3Weiming Xia4Jianhua Zhang5Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, CanadaDepartments of Psychiatry, Chemistry, Pharmacology and Toxicology, University of Toronto, Toronto, ON, CanadaGeriatric Research Education and Clinical Center, Bedford VA Healthcare System, Bedford, MA, United StatesDepartment of Pharmacology, Physiology and Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, United StatesDepartment of Biological Sciences, University of Massachusetts Kennedy College of Science, Lowell, MA, United StatesDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL, United StatesAlzheimer’s disease (AD) is the most common age-related neurodegenerative disease and cause of dementia. AD pathology primarily involves the formation of amyloid β (Aβ) plaques and neurofibrillary tangles containing hyperphosphorylated tau (p-tau). While Aβ targeted treatments have shown clinical promise, other aspects of AD pathology such as microgliosis, astrocytosis, synaptic loss, and hypometabolism may be viable targets for treatment. Among notable novel therapeutic approaches, the Ras homolog (Rho)-associated kinases (ROCKs) are being investigated as targets for AD treatment, based on the observations that ROCK1/2 levels are elevated in AD, and activation or inhibition of ROCKs changes dendritic/synaptic structures, protein aggregate accumulation, inflammation, and gliosis. This review will highlight key findings on the effects of ROCK inhibition in Aβ and ptau pathologies, as well as its effects on neuroinflammation, synaptic density, and potentially metabolism and bioenergetics.https://www.frontiersin.org/articles/10.3389/fragi.2025.1547883/fullAlzheimer’s diseasefasudilamyloidphosphorylated tauglucose metabolismPET imaging
spellingShingle Chao Zheng
Chao Zheng
Weiming Xia
Weiming Xia
Weiming Xia
Jianhua Zhang
Rock inhibitors in Alzheimer’s disease
Frontiers in Aging
Alzheimer’s disease
fasudil
amyloid
phosphorylated tau
glucose metabolism
PET imaging
title Rock inhibitors in Alzheimer’s disease
title_full Rock inhibitors in Alzheimer’s disease
title_fullStr Rock inhibitors in Alzheimer’s disease
title_full_unstemmed Rock inhibitors in Alzheimer’s disease
title_short Rock inhibitors in Alzheimer’s disease
title_sort rock inhibitors in alzheimer s disease
topic Alzheimer’s disease
fasudil
amyloid
phosphorylated tau
glucose metabolism
PET imaging
url https://www.frontiersin.org/articles/10.3389/fragi.2025.1547883/full
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AT weimingxia rockinhibitorsinalzheimersdisease
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