NFKF is a synthetic fragment derived from rat hemopressin that protects mice from neurodegeneration

Andrea S Heimann; A C Giardini; M B Sant'Anna; Nilton B Dos Santos; Mayara C F Gewehr; Carolina D Munhoz; Leandro M Castro; Gisele Picolo; Ricardo A Remer; Emer S Ferro

doi:10.1016/j.neulet.2020.134765

NFKF is a synthetic fragment derived from rat hemopressin that protects mice from neurodegeneration

Neurosci Lett. 2020 Mar 16:721:134765. doi: 10.1016/j.neulet.2020.134765. Epub 2020 Jan 28.

Authors

Affiliations

¹ Proteimax Biotechnology, 05581001, São Paulo, Brazil.
² Special Laboratory of Pain and Signaling, Butantan Institute, São Paulo, 05503-900, Brazil.
³ Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, 05508-900, São Paulo, Brazil.
⁴ Biosciences Institute, São Paulo State University, 11330-900, São Vicente, Brazil.
⁵ Remer Consultores Ltda., São Paulo, 01411-001, SP, Brazil.
⁶ Department of Pharmacology, Biomedical Sciences Institute, University of São Paulo, 05508-900, São Paulo, Brazil. Electronic address: eferro@usp.br.

PMID: 32004656
DOI: 10.1016/j.neulet.2020.134765

Abstract

Previous studies suggested the pharmacological potential of rat hemopressin (PVNFKFLSH) and its shorter synthetic peptide NFKF, to protect from pilocarpine-induced seizures in mice. Orally administered NFKF was shown to be hundred times more potent than cannabidiol in delaying the first seizure induced by pilocarpine in mice. Here, using an experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis we have shown that C57BL/6 J mice orally administrated with NFKF (500 μg/kg) presented better EAE clinical scores and improved locomotor activity compared to saline administrated control mice. NFKF blocked the production of IL-1beta and IL-6, and has high scores binding cannabinoid type 2 receptors. Therefore, NFKF is an exciting new possibility to neurodegenerative diseases therapeutics.

Keywords: Cannabinoid; EAE; Intracellular peptides; Neurodegenerative diseases.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines / antagonists & inhibitors
Cytokines / metabolism
Encephalomyelitis, Autoimmune, Experimental / metabolism*
Encephalomyelitis, Autoimmune, Experimental / pathology
Encephalomyelitis, Autoimmune, Experimental / prevention & control*
Female
Hemoglobins / chemistry
Hemoglobins / pharmacology
Hemoglobins / therapeutic use*
Mice
Mice, Inbred C57BL
Molecular Docking Simulation / methods
Neuroprotective Agents / chemistry
Neuroprotective Agents / pharmacology
Neuroprotective Agents / therapeutic use*
Peptide Fragments / chemistry
Peptide Fragments / pharmacology
Peptide Fragments / therapeutic use*
Rats

Substances

Cytokines
Hemoglobins
Neuroprotective Agents
Peptide Fragments
hemopressin