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Cited by 27Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment Research

Therapeutic effect of Rho kinase inhibitor FSD‑C10 in a mouse model of Alzheimer's disease

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Gu, Qing‑Fang, Yu, Jie‑Zhong, Wu, Hao, Li, Yan‑Hua, Liu, Chun-Yun, Feng, Ling, Zhang, Guang‑Xian, Xiao, Bao‑Guo +1 more·2018·Experimental and Therapeutic Medicine
DOI 10.3892/etm.2018.6701PMC PMC6176147
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Abstract

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer's disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long‑term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long‑term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD‑C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin‑1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of its action. The results showed that FSD‑C10 effectively improved learning and memory impairment, accompanied by reduced expression of amyloid‑β 1‑42 (Aβ1‑42), Tau protein phosphorylation (P‑tau) and β‑site APP‑cleaving enzyme in the hippocampus and cortex area of brain. In addition, FSD‑C10 administration boosted the expression of synapse‑associated proteins, such as postynaptic density protein 95, synaptophsin, α‑amino 3‑hydroxy‑5‑methyl‑4‑isoxa‑zolep‑propionate receptor and neurotrophic factors, e,g., brain‑derived neurotrophic factor and glial cell line‑derived neurotrophic factor. Taken together, our results demonstrate that FSD‑C10 has therapeutic potential in the AD mouse model, possibly through inhibiting the formation of Aβ1‑42 and P‑tau, and promoting the generation of synapse‑associated proteins and neurotrophic factors.

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  • ROCK inhibition in an APP/presenilin-1 transgenic mouse model improves learning and memory impairment, accompanied by reduced tau phosphorylation, expression of Aβ and BACE1, and increased expression of synapse-associated proteins and neurotrophic factors in the hippocampus and cortex.

    “ROCK inhibition in an APP/presenilin-1 (PS1) transgenic mouse model showed improved learning and memory impairment, accompanied by reduced tau phosphorylation, expression of Aβ and BACE1, and increased expression of synapse-associated proteins and neurotrophic factors in the hippocampus and cortex area of the brain [192].”

    From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [192]

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Authors
Gu, Q., Yu, J., Wu, H., Li, Y., Liu, C.-Y., Feng, L., Zhang, G., Xiao, B., & Ma, C.
Affiliations
  • Department of Neurology, Institute of Brain Science, Medical School, Shanxi Datong University, Datong, Shanxi 037009, P.R. China
  • Shanxi Datong University (CN)
  • Thomas Jefferson University (US)
  • Shanghai Medical College of Fudan University (CN)
Corresponding author
  • Xiao, Bao‑Guo
  • Ma, Cun‑Gen
ORCID
Venue
Experimental and Therapeutic Medicine
Publisher
Spandidos Publications
Published
2018-09-05
Volume
16
Issue
5
Pages
3929-3938
ISSN
  • 1792-0981 (ISSN-L)
  • 1792-1015
DOI
10.3892/etm.2018.6701
PMC
PMC6176147
OpenAlex
W2891245331
Cited by
27
References
4
Citations by year
2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 3
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Experimental and Therapeutic Medicine (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • The Medicine Forum (submittedVersion, cc-by-nc-nd)
Funders
  • Thomas Jefferson University
  • National Natural Science Foundation of China (81371414, 81272163, 81471412)
  • Shanxi Datong University
  • Shanxi University
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
ROCK inhibitor, Alzheimer's disease, APP/PS1 mice, amyloid-beta 42, tau phosphorylation, BACE1, learning and memory impairment, synaptic proteins, PSD-95, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, neurotrophic factors, hippocampus, cortex

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