The Rho kinase inhibitor fasudil attenuates Aβ1–42-induced apoptosis via the ASK1/JNK signal pathway in primary cultures of hippocampal neurons

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal

View graph of relations

Author(s)

  • Ye Gao
  • Yuqing Yan
  • Qingli Fang
  • Nianping Zhang
  • Gajendra Kumar
  • And 6 others
  • Jihong Zhang
  • Li-Juan Song
  • Jiezhong Yu
  • Linhu Zhao
  • Han-Ting Zhang
  • Cun-Gen Ma

Related Research Unit(s)

Detail(s)

Original languageEnglish
Pages (from-to)1787-1801
Journal / PublicationMetabolic Brain Disease
Volume34
Issue number6
Online published3 Sep 2019
Publication statusPublished - Dec 2019

Abstract

Alzheimer’s disease (AD), a chronic, progressive, neurodegenerative disorder, is the most common type of dementia. Beta amyloid (Aβ) peptide aggregation and phosphorylated tau protein accumulation are considered as one of the causes for AD. Our previous studies have demonstrated the neuroprotective effect of the Rho kinase inhibitor fasudil, but the mechanism remains elucidated. In the present study, we examined the effects of fasudil on Aβ1–42 aggregation and apoptosis and identified the intracellular signaling pathways involved in these actions in primary cultures of mouse hippocampal neurons. The results showed that fasudil increased neurite outgrowth (52.84%), decreased Aβ burden (46.65%), Tau phosphorylation (96.84%), and ROCK-II expression. In addition, fasudil reversed Aβ1–42-induced decreased expression of Bcl-2 and increases in caspase-3, cleaved-PARP, phospho-JNK(Thr183/Tyr185), and phospho-ASK1(Ser966). Further, fasudil decreased mitochondrial membrane potential and intracellular calcium overload in the neurons treated with Aβ1–42. These results suggest that inhibition of Rho kinase by fasudil reverses Aβ1–42-induced neuronal apoptosis via the ASK1/JNK signal pathway, calcium ions, and mitochondrial membrane potential. Fasudil could be a drug of choice for treatment of Alzheimer’s disease.

Research Area(s)

  • Alzheimer’s disease, Apoptosis, Aβ1–42, Fasudil, JNK, Neurons, Rho kinase

Citation Format(s)

The Rho kinase inhibitor fasudil attenuates Aβ1–42-induced apoptosis via the ASK1/JNK signal pathway in primary cultures of hippocampal neurons. / Gao, Ye; Yan, Yuqing; Fang, Qingli; Zhang, Nianping; Kumar, Gajendra; Zhang, Jihong; Song, Li-Juan; Yu, Jiezhong; Zhao, Linhu; Zhang, Han-Ting; Ma, Cun-Gen.

In: Metabolic Brain Disease, Vol. 34, No. 6, 12.2019, p. 1787-1801.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journal