Tetracyclines and prion infectivity

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

In the last decade information has accumulated on the potential anti-prion activity of polycyclic compounds. Initially we showed that the antitumoral idodoxorubicin reduced the infectivity in experimental scrapie. On the basis of the chemical homology with anthracyclines, we rapidly moved to tetracyclines, compounds that are safer and widely used as antibiotics in clinical practice. The tetracyclines, essentially doxycycline and minocycline, were characterized as a therapeutical tool in transmissible spongiform encephalopathies (TSE) through the cell-free condition, in cellular and animal models and they are now being investigated clinically with this indication. Tetracyclines interact with aggregates obtained by synthetic PrP peptides or pathological PrP (PrPsc) extracted from TSE brains, and they destabilize the structure of amyloid fibrils, reducing their resistance to digestion by proteinase K. Tetracyclines also interact with peptide oligomeric structures and inhibit the protein misfolding associated with PrPsc formation. These activities have been accompanied by a reduction of infectivity, verified by doxycycline treatment in experimental scrapie, and some curative effects after either peripheral or intracerebral infection. The anti-amyloidogenic activity of tetracyclines was tested in other forms of peripheral and central amyloidosis, with interesting results. This article analyzes the development of tetracyclines as a therapeutic tool in TSE in the light of recent results obtained in our laboratories.

Original languageEnglish
Pages (from-to)23-30
Number of pages8
JournalInfectious Disorders - Drug Targets
Volume9
Issue number1
Publication statusPublished - 2009

Fingerprint

Tetracyclines
Prions
Prion Diseases
Scrapie
Doxycycline
Polycyclic Compounds
Endopeptidase K
Peptides
Minocycline
Anthracyclines
Amyloidosis
Amyloid
Digestion
Animal Models
Anti-Bacterial Agents
Brain
Infection
Proteins

ASJC Scopus subject areas

  • Molecular Medicine
  • Microbiology (medical)
  • Pharmacology

Cite this

Tetracyclines and prion infectivity. / Forloni, Gianluigi; Salmona, Mario; Mareon, Gabriella; Tagliavini, Fabrizio.

In: Infectious Disorders - Drug Targets, Vol. 9, No. 1, 2009, p. 23-30.

Research output: Contribution to journalArticle

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