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

Applied Microbiology and Biotechnology
Meizhu WangHongyu Li

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 re...Continue Reading

References

Mar 1, 1985·Peptides·M Holdeman, J M Lipton
Feb 13, 2001·The Journal of Clinical Investigation·M P Mattson, S Camandola
Jun 8, 2002·Science·Ellen E PaxinosRobert C Fleischer
Jun 19, 2002·Pharmaceutical Research·Victor Tuan Giam ChuangMasaki Otagiri
Jul 20, 2002·Brain Research. Developmental Brain Research·Ellen G DuysenOksana Lockridge
Jan 31, 2003·American Journal of Physiology. Endocrinology and Metabolism·Ira Gantz, Tung M Fong
Mar 6, 2004·Pharmacological Reviews·Anna CataniaJames M Lipton
Dec 24, 2004·Diabetes·Alokesh DuttaroyOlivier Blondel
Apr 27, 2005·Brain Research. Brain Research Reviews·Milla Koistinaho, Jari Koistinaho
Jan 13, 2006·British Journal of Pharmacology·Sian-Marie LucasRosemary M Gibson
Mar 17, 2006·Journal of Neuroscience Research·Tammy Kielian
Oct 17, 2006·Journal of Leukocyte Biology·Anna Catania
Oct 5, 2007·Trends in Molecular Medicine·Jacob M Gump, Steven F Dowdy
Oct 24, 2007·Journal of Molecular Neuroscience : MN·Asa Forslin AronssonMarianne Schultzberg
Nov 15, 2007·Applied Microbiology and Biotechnology·Yadong HuangXiaokun Li
Dec 11, 2007·Nature Biotechnology·G Mani SubramanianJohn G McHutchison
Dec 21, 2007·Advanced Drug Delivery Reviews·Sadamitsu Asoh, Shigeo Ohta
Jun 14, 2008·Trends in Neurosciences·Anna Catania
Jun 28, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Felix Kratz
Oct 8, 2008·Journal of Neuroimmunology·Ethika TyagiRakesh Shukla
Jan 20, 2009·Biological Psychiatry·Andrew H MillerCharles L Raison
May 5, 2010·CNS Neuroscience & Therapeutics·Zsigmond Tamas Kincses, Laszlo Vecsei
Jun 18, 2010·Neurobiology of Disease·Thorsten R DoeppnerMathias Bähr
Sep 21, 2010·TheScientificWorldJournal·Anna CataniaStefano Gatti
Dec 9, 2010·The Journal of Biological Chemistry·Jan Terje AndersenCaroline Ekblad
May 20, 2011·Reviews in the Neurosciences·Kanaiyalal D PrajapatiNilanjan Roy
Jun 1, 2011·FEBS Letters·Bente Finsen, Trevor Owens
Jan 11, 2012·Molecular Aspects of Medicine·Gabriella FanaliPaolo Ascenzi
Apr 26, 2012·Frontiers in Neuroendocrinology·Daniela GiulianiSalvatore Guarini
Jun 26, 2012·Brain, Behavior, and Immunity·Alok Kumar, David J Loane
Aug 1, 2012·Experimental & Molecular Medicine·Hoon Jae JeongSoo Young Choi
Oct 2, 2012·International Journal of Biological Macromolecules·Masahiro TsubakiAkiko Koga
Oct 3, 2012·Advanced Drug Delivery Reviews·Xiaoying ChenWei-Chiang Shen
Oct 31, 2012·International Journal of Molecular Sciences·Jens MinnerupChristoph Kleinschnitz
Jun 6, 2013·International Journal of Inflammation·Tazeen J AhmedCostantino Pitzalis
Sep 3, 2014·Journal of Neuroinflammation·David J Allison, David S Ditor
Jan 8, 2015·The Annals of Pharmacotherapy·Angela M Thompson, Jennifer M Trujillo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Acute Stroke

A stroke occurs when blood supply to the brain is interrupted depriving the brain of oxygen and nutrients. This feed focuses cerebrovascular accidents including ischemic and paralytic stroke.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier & Cytokines

Some cytokines are able to cross the blood brain barrier through transport systems and enter the cerebrospinal fluid and interstitial fluid spaces. Here is the latest research on cytokines crossing the blood brain barrier and how this can affect tissues within the CNS.

Brain Injury & Trauma

brain injury after impact to the head is due to both immediate mechanical effects and delayed responses of neural tissues.