The role of fasudil treatment on amyloid beta induced inflammation model in astrocytes

Alzheimer's disease is the most common neurodegenerative disorder to date. Neuropathological features is amyloid plaque and neurofibrillary tangles. However, the inflammatory process has a fundamental role in the pathogenesis of Alzheimer's disease. Cytokines play a key role in inflammatory and anti-inflammatory processes in Alzheimer's disease. Recently, a large number of apoptotic regulatory factors and multiple pathways have been identified, and apoptotic cell death has been associated with neuronal loss in Alzheimer's disease. Rho-kinase is overactivated in many CNS disorders and inhibition of rho is thought to be a potential therapeutic agent in inflammatory and demyelinating diseases. Fasudil is a rho-kinase inhibitor and has neuroprotective effects. The main purpose of this thesis is to investigate whether fasudil is beneficial for beta amyloid induced neuronal toxicity. In this study, it was aimed to contribute to current literature about whether pharmacological approach to Alzheimer's disease of amyloid beta induced inflammation in the astrocyte cell line would be fasudil. Cells were incubated with 5 μM amyloid beta for 24 hours. Another group of rho kinase inhibitors for treatment was added to 2,5 μM fasudil. cDNA synthesis was performed from RNA samples isolated from the cells. Gene expression analysis was performed by real-time PCR method. According the results obtained, amyloid beta TNF-α, IL-1β, IL-6, IL-10, IL-12, Cas-3, Cas-8, Bax, Bcl-2 mRNA expression levels were 2 to 27 higher than control group. Fasudil therapy significantly reduced the increase in amyloid beta-stimulated inflammation and some apoptotic genes. (p<0.001). Microscopic examinations also showed of fasudil cell protective effect. As a result, the inhibition of rho kinase by fasudil may be an agent that can be used in therapy with a protective effect on the suppression of amyloid beta mediated inflammation. However, further work is needed to arrive at a definite conclusion. Key Words: Alzheimer's disease, Amyloid beta, Fasudil, TNF-α, Cas-3, Cas-8