Open Access

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

  • Authors:
    • Qing‑Fang Gu
    • Jie‑Zhong Yu
    • Hao Wu
    • Yan‑Hua Li
    • Chun-Yun Liu
    • Ling Feng
    • Guang‑Xian Zhang
    • Bao‑Guo Xiao
    • Cun‑Gen Ma
  • View Affiliations

  • Published online on: September 5, 2018     https://doi.org/10.3892/etm.2018.6701
  • Pages: 3929-3938
  • Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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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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November-2018
Volume 16 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Gu QF, Yu JZ, Wu H, Li YH, Liu C, Feng L, Zhang GX, Xiao BG and Ma CG: Therapeutic effect of Rho kinase inhibitor FSD‑C10 in a mouse model of Alzheimer's disease. Exp Ther Med 16: 3929-3938, 2018.
APA
Gu, Q., Yu, J., Wu, H., Li, Y., Liu, C., Feng, L. ... Ma, C. (2018). Therapeutic effect of Rho kinase inhibitor FSD‑C10 in a mouse model of Alzheimer's disease. Experimental and Therapeutic Medicine, 16, 3929-3938. https://doi.org/10.3892/etm.2018.6701
MLA
Gu, Q., Yu, J., Wu, H., Li, Y., Liu, C., Feng, L., Zhang, G., Xiao, B., Ma, C."Therapeutic effect of Rho kinase inhibitor FSD‑C10 in a mouse model of Alzheimer's disease". Experimental and Therapeutic Medicine 16.5 (2018): 3929-3938.
Chicago
Gu, Q., Yu, J., Wu, H., Li, Y., Liu, C., Feng, L., Zhang, G., Xiao, B., Ma, C."Therapeutic effect of Rho kinase inhibitor FSD‑C10 in a mouse model of Alzheimer's disease". Experimental and Therapeutic Medicine 16, no. 5 (2018): 3929-3938. https://doi.org/10.3892/etm.2018.6701