Burçin Nilay Yener, Necla Benlier, Hülya Çicek
Objective: Alzheimer's disease is a progressive neurodegenerative disorder with characteristic neuropathological changes. Neuropathological hallmarks of Alzheimer's disease include amyloid plaques and neurofibrillary tangles. 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.
Rho-kinase is overactivated in many CNS disorders and its inhibition could be a potential therapeutic target for inflammatory and demyelinating diseases. Fasudil is a Rho-kinase inhibitor and has neuroprotective effects.
Methods: We aimed to investigate whether fasudil treatment represents a pharmacological approach in Alzheimer's disease by examining its effects in amyloid beta- induced inflammation in a murine astrocyte cell line and to contribute to existing literature.
Astrocytes were incubated with 5 μM amyloid beta for 24 hours. Another group of astrocytes was treated with Fasudil, a Rho kinase inhibitor, at a dose of 2,5 μM in addition to amyloid beta. cDNA synthesis was performed on RNA samples isolated from the cells. Gene expression analysis was conducted using real-time PCR methodology.
Results: Amyloid beta increased Tumor necrosis factor (TNF-α), IL-1β, IL-6, IL-10, IL-12, Cas-3, Cas-8, Bcl2- associated X protein (Bax) and B-cell CLL/lymphoma 2 (Bcl-2) mRNA expression levels 2 to 27-fold compared to control group. Fasudil treatment significantly reduced the increase in amyloid beta-induced inflammation and some apoptotic genes studied. (p<0.001).
Conclusion: Inhibition of Rho kinase by fasudil may be a potential treatment target owing to its protective effect against amyloid beta-mediated inflammation. However, further studies are needed to corroborate our preliminary findings.View pdf