TAT-HSA-α-MSH fusion protein with extended half-life inhibits tumor necrosis factor-α in brain inflammation of mice
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Neuroinflammation constitutes a principal process involved in the progression of various central nervous system (CNS) disorders, including Parkinson’s disease, Alzheimer’s disease, ischemic stroke, and traumatic brain injury. The safety and efficacy of potential neuroprotective therapeutic agents is controversial and limited. Alpha-melanocyte-stimulating hormone (α-MSH) as a tridecapeptide derived from pro-opiomelanocortin displays potent anti-inflammatory and protective effects with a wide therapeutic window in brain damage. However, it is difficult to deliver effective concentrations of α-MSH into brain tissue via nondirect application. Besides, the half-life of the tridecapeptide is only a few minutes. In the present study, we generated a novel TAT-HSA-α-MSH by genetically fusing α-MSH with N-terminus 11-amino acid protein transduction domain of the human immunodeficiency virus Tat protein (TAT) and human serum albumin (HSA), which showed favorable pharmacokinetic properties and can effectively cross the blood brain barrier (BBB). The findings showed that TAT-HSA-α-MSH significantly inhibits NF-κB activation in human glioma cells A172 and tumor necrosis factor-α (TNF-α) production in experimental brain inflammation. These results indicate that TAT-HSA-α-MSH may be a potential therapeutic agent for treating neuroinflammation which plays a fundamental role in CNS disorders.
KeywordsHalf-life Neuroinflammation Blood brain barrier TAT-HSA-α-MSH
This study was supported by the special international cooperation project of Ministry of Science and Technology (2012DFA30480); the key project of Gansu Province science and technology (1002WKDE055); Gansu Province Scientific Research Project Fund (090WCGA900). Fundamental Research Funds for the Central Universities of China (lzujbky-2014-147).
Compliance with ethical standards
The whole experiments involving mice were approved by the Ethics Committee of Experimental Animals of Lanzhou University and carried out in accordance with the Guide for the Care and Use of Laboratory Animals.
Conflict of interest
The authors declare that they have no competing interests.
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