Bacterial Toxins and Targeted Brain Therapy: New Insights from Cytotoxic Necrotizing Factor 1 (CNF1)

Int J Mol Sci. 2018 May 31;19(6):1632. doi: 10.3390/ijms19061632.

Abstract

Pathogenic bacteria produce toxins to promote host invasion and, therefore, their survival. The extreme potency and specificity of these toxins confer to this category of proteins an exceptionally strong potential for therapeutic exploitation. In this review, we deal with cytotoxic necrotizing factor (CNF1), a cytotoxin produced by Escherichia coli affecting fundamental cellular processes, including cytoskeletal dynamics, cell cycle progression, transcriptional regulation, cell survival and migration. First, we provide an overview of the mechanisms of action of CNF1 in target cells. Next, we focus on the potential use of CNF1 as a pharmacological treatment in central nervous system's diseases. CNF1 appears to impact neuronal morphology, physiology, and plasticity and displays an antineoplastic activity on brain tumors. The ability to preserve neural functionality and, at the same time, to trigger senescence and death of proliferating glioma cells, makes CNF1 an encouraging new strategy for the treatment of brain tumors.

Keywords: CNF1; Rho GTPases; cerebral cortex; glioma; plasticity.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / pharmacology*
  • Bacterial Toxins / therapeutic use*
  • Brain Diseases / drug therapy*
  • Brain Diseases / etiology*
  • Brain Diseases / metabolism
  • Brain Diseases / pathology
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / pharmacology
  • Escherichia coli Proteins / therapeutic use
  • Gene Expression Regulation / drug effects
  • Humans
  • Molecular Targeted Therapy*
  • Neurons / drug effects
  • Neurons / metabolism
  • Signal Transduction / drug effects
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Bacterial Toxins
  • Escherichia coli Proteins
  • cytotoxic necrotizing factor type 1