Diagnostic and therapeutic potential of tetanus toxin-derivatives in neurological diseases

R. Kassa, V. Monterroso, L. L. David, D. Tshala-Katumbay

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

We assessed the ex vivo reactivity of peptidic constructs of Tet1 (analog of tetanus toxin non-virulent C fragment) with sequence homology to the cysteine-active site of thioredoxin (Tet1THO) or tetralysine (Tet1PLYS) with oxidative species or axonopathic sodium cyanate (NaOCN), respectively. We then assessed their neuronal uptake in vivo in laboratory animals. The reactivity of Tet1PLYS with NaOCN (1:2.5 to 1:37.5 molar ratios) or Tet1THO with hydrogen peroxide (1:0.4 to 1:6.2 molar ratios) was assessed by mass spectrometry. Green fluorescence protein (GFP)-tagged Tet1-derivatives (3 mg/ml in artificial cerebrospinal fluid) were administered daily to rats by intramuscular injection in latissimus dorsi at lumborum at the dose of 1 μl/g of body weight, for 3 days. Motor neuron uptake was assessed after double immunolabeling for GFP and choline acetyltransferase. Mass spectrometry analysis successfully demonstrated the ex vivo reactivity of Tet1-derivatives in a concentration-dependent manner. Confocal microscopy revealed the localization of Tet1-derivatives in axons and motor neuron cell bodies. Intramuscular delivery of Tet1-derivatives appears to be a practical approach to circumvent the blood nerve barrier and selectively deliver small molecules to the nervous system, for diagnostic and/or treatment purposes.

Original languageEnglish (US)
Pages (from-to)788-791
Number of pages4
JournalJournal of Molecular Neuroscience
Volume51
Issue number3
DOIs
StatePublished - Nov 2013

Keywords

  • Axonal transport
  • Blood nerve barrier
  • Drug delivery
  • Neurodegeneration
  • Neurotoxicity
  • Tetanus toxin

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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