title: TAT-HSA-α-MSH fusion protein with extended half-life inhibits tumor necrosis factor-α in brain inflammation of mice.
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.
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui Road No. 222, Lanzhou, 730000, People's Republic of China.
authors.forename: Meizhu
authors.initials: M
authors.lastname: Wang
authors.affiliation: Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Dejuan
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui Road No. 222, Lanzhou, 730000, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ru
authors.affiliation: Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ren
authors.affiliation: Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui Road No. 222, Lanzhou, 730000, People's Republic of China.
authors.forename: Yiyao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Institute of Microbiology, School of Life Sciences, Lanzhou University, Tianshui Road No. 222, Lanzhou, 730000, People's Republic of China. lihy@lzu.edu.cn.|Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou, People's Republic of China. lihy@lzu.edu.cn.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004660:Encephalitis / Q000188:drug therapy* / Q000378:metabolism; D005786:Gene Expression Regulation; D006207:Half-Life; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000521:alpha-MSH / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics* / Q000494:pharmacology*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics
chemical_list: D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus; D000521:alpha-MSH
keywords: Blood brain barrier; Half-life; Neuroinflammation; TAT-HSA-α-MSH