title: Rho kinase inhibitor fasudil protects against β-amyloid-induced hippocampal neurodegeneration in rats.
abstract: OBJECTIVE
  Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and Aβ-induced neuronal damage is the major pathology of AD. There is increasing evidence that neuroinflammation induced by Aβ is also involved in the pathogenesis of AD. Fasudil is a Rho kinase inhibitor and has been reported to have neuroprotective effects. In this study, the main purpose is to investigate whether fasudil has beneficial effects on cognitive impairment and neuronal toxicity induced by Aβ.
  
  
  RESULTS
  In the present study, intracerebroventricular injection of Aβ1-42 to rats resulted in marked cognitive impairment, severe neuronal damage, as well as increased IL-1β, tumor necrosis factor alpha (TNF-α) production, and NF-κB activation. Administration of fasudil significantly ameliorated the spatial learning and memory impairment, attenuated neuronal loss, and neuronal injury induced by Aβ1-42 . In addition, fasudil inhibited IL-1β and TNF-α production and NF-κB activation in the rat brain.
  
  
  CONCLUSIONS
  Fasudil can protect against Aβ-induced hippocampal neurodegeneration by suppressing inflammatory response, suggesting that fasudil might be a promising agent for the prevention and treatment of inflammation-related diseases, such as AD.
authors: Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
authors: Yun
authors: Y
authors: Song
authors: Xu
authors: X
authors: Chen
authors: Li-Yan
authors: LY
authors: Wang
authors: Wei
authors: W
authors: Gao
authors: Mei-Jia
authors: MJ
authors: Zhu
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D047428:Protein Kinase Inhibitors; C075222:amyloid beta-protein (1-42); D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil
keywords: Alzheimer's disease; Neuroinflammation; Rho kinase inhibitor; β-amyloid
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