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Can a Drug Approved for CML Affect Treatment of Degenerative Brain Diseases?

By: Cordi Craig
Posted: Thursday, November 21, 2019

The small-molecule inhibitor of tyrosine kinases dasatinib may affect lipopolysaccharide-induced microglial and astrocytic neuroinflammation through signaling the AKT/STAT3 pathways. Hyang-Sook Hoe, PhD, and colleagues at the Korea Brain Research Institute, Daegu, South Korea, suggest that when taken orally or through intraperitoneal injection, this drug used to treat chronic myeloid leukemia (CML) appears to reduce lipopolysaccharide-induced microglial activation, proinflammatory cytokine levels, and neutrophil rolling in the brain. Because encephalitis may be associated with degenerative brain diseases and the activation of microglial cells causes nerve damage and memory degeneration, the report, published in the Journal of Neuroinflammation, suggests that dasatinib may affect the treatment of brain diseases, such as Alzheimer’s disease and dementia.

The researchers used BV2 microglial cells to measure the effects of dasatinib on lipopolysaccharide-induced neuroinflammation. Dasatinib was also administered to mice to analyze how the drug affects lipopolysaccharide-induced microglial/astrocyte activation, proinflammatory cytokine levels, and neutrophil rolling.

Dasatinib appears to regulate lipopolysaccharide-induced proinflammatory cytokine and anti-inflammatory cytokine levels in BV2 microglial cells, primary microglial cells, and primary astrocytes. The proinflammatory cytokine levels are regulated by TLR4/AKT and TLR4/ERK signaling. In the mouse model, dasatinib induced encephalitis and reduced microglial cell activity, neutrophil rolling in the brain, and proinflammatory cytokine expression in the brain and plasma. 

“In the follow-up research, we will study the possibility of dasatinib as a multitarget medicine that can simultaneously control several pathologies of Alzheimer’s disease,” Dr. Hoe stated in a press release from the Korea Brain Research Institute.

Disclosure: The study authors reported no conflicts of interest.



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