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Applied Microbiology and Biotechnology

, Volume 100, Issue 12, pp 5353–5361 | Cite as

TAT-HSA-α-MSH fusion protein with extended half-life inhibits tumor necrosis factor-α in brain inflammation of mice

  • Meizhu Wang
  • Dejuan Zhi
  • Haiqing Wang
  • Yi Ru
  • Hui Ren
  • Na Wang
  • Yiyao Liu
  • Yang Li
  • Hongyu LiEmail author
Biotechnological products and process engineering

Abstract

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.

Keywords

Half-life Neuroinflammation Blood brain barrier TAT-HSA-α-MSH 

Notes

Acknowledgments

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Meizhu Wang
    • 1
  • Dejuan Zhi
    • 2
  • Haiqing Wang
    • 2
  • Yi Ru
    • 1
  • Hui Ren
    • 2
  • Na Wang
    • 2
  • Yiyao Liu
    • 1
  • Yang Li
    • 2
  • Hongyu Li
    • 1
    • 2
    Email author
  1. 1.Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Institute of Microbiology, School of Life SciencesLanzhou UniversityLanzhouPeople’s Republic of China
  2. 2.Gansu High Throughput Screening and Creation Center for Health Products, School of PharmacyLanzhou UniversityLanzhouPeople’s Republic of China

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