title: 4-iodophenyl isothiocyanate: a neuroprotective compound.
abstract: OBJECTIVE
  Naturally occurring isothiocyanates (ITCs) are known to possess chemopreventive and neuroprotective properties. Our objective was to study the synthetic ITC 4-iodophenyl isothiocyanate (4-IPITC) in different models of neurodegeneration.
  
  
  METHODS
  In vitro, we exposed primary cortical neurons to various insults such as excessive glutamate exposure, oxygen-glucose deprivation, oxidative stress and 1-methyl-phenylpyridinium (MPP+). In vivo, experimental autoimmune encephalomyelitis (EAE) was induced in dark agouti rats treated with 4-IPITC in 3 different concentrations (10, 20 and 40 mg/kg), orally for 28 days. In a Parkinson's model, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected in mice pretreated with 4-IPITC (5 mg/kg, orally) for 1 week. Nest building behavior at day 1, 3 and 6 after MPTP injection was assessed along with dopamine and metabolites, and tyrosine hydroxylase (TH) staining on termination day 6.
  
  
  RESULTS
  4-IPITC successfully reduced cell death in all in vitro assays. Moreover, in two independent neurite outgrowth assays the compound showed neurotrophic properties. In the EAE study, 4-IPITC significantly delayed the day of onset and decreased the cumulative EAE score. Although the number of animals in this MPTP study was limited, 4-IPITC showed potential for dampening toxicity.
  
  
  CONCLUSIONS
  Taken together, our in vitro findings suggest robust neuroprotective and neurotrophic properties of 4-IPITC, which was confirmed in two in vivo models of neurodegeneration.
authors.affiliation: Nensius Research A/S, Symbion Science Park, Fruebjergvej, Copenhagen, Denmark. anja.wellejus@gmail.com
authors.forename: Anja
authors.initials: A
authors.lastname: Wellejus
authors.forename: Heidi
authors.initials: H
authors.lastname: Elbrønd-Bek
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Kelly
authors.forename: Morten S
authors.initials: MS
authors.lastname: Weidner
authors.forename: Signe H
authors.initials: SH
authors.lastname: Jørgensen
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000494:pharmacology; D006540:Herbicides / Q000633:toxicity; D000860:Hypoxia / Q000188:drug therapy; D007462:Iodobenzenes / Q000494:pharmacology*; D017879:Isothiocyanates / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008995:Monoamine Oxidase / Q000378:metabolism; D016202:N-Methylaspartate / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010545:Peroxides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D006540:Herbicides; D007462:Iodobenzenes; D017879:Isothiocyanates; D018696:Neuroprotective Agents; D010545:Peroxides; C052479:4-iodophenylisothiocyanate; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D008995:Monoamine Oxidase; D005947:Glucose; D015655:1-Methyl-4-phenylpyridinium