THE ONE CLICK GROUP
www.theoneclickgroup.co.uk
Email mail@theoneclickgroup.co.uk
17 September 2006
Amyloid Fibrils and PrP-Priority Lyme Disease Investigation
From Lara
Tetracycline inactivates the pathogenic forms of Prioin Protein
(PrP)
This information, published over 6 years ago is truly fascinating. Amyloid
Fibrils, (insoluble fibrous proteins that can result from the presence of
prion proteins (PrP)) are found in the brains of many neurological
diseases where borrelia bacteria have also been considered to play a role
e.g. Alzheimer's and Parkinson's.
Interestingly, this research group found that the antibiotic - tetracycline
often used to treated chronic borreliosis/Lyme had a therapeutic effect in
reducing the pathogenecity of these same PrP.
Considering that Amyloid Fibrils and PrP are significant areas of scientific
study for many neurological diseases, shouldn't any possible role of these
substances in those diagnosed with Lyme disease and/or ME/CFS be
investigated as a matter of priority?
BW
Lara
Journal of Molecular Biology
Volume 300, Issue 5 , 28 July 2000, Pages 1309-1322
Tetracycline affects abnormal properties of synthetic PrP peptides
and PrPSc in vitro1
Fabrizio Tagliavini1, Gianluigi Forloni2, Laura Colombo2, Giacomina
Rossi1, Laura Girola2, Barbara Canciani1, Nadia Angeretti2, Lidia
Giampaolo1, Elisa Peressini2, Tazeen Awan1, Luca De Gioia3, Enzio
Ragg4, Orso Bugiani1 and Mario Salmona, , 2
1 Istituto Nazionale Neurologico Carlo Besta, Via Celoria 11 20133,
Milano, Italy
2 Department of Biochemistry and Molecular Pharmacology and
Department of Neurology Istituto di Ricerche Farmacologiche Mario Negri
Via Eritrea 62, 20157, Milano, Italy
3 Dipartimento di Biotecnologie e Bioscienze, Università di MilanoBicocca, Piazza Della Scienza 2, 20126, Milano, Italy
4 Dipartimento di Scienze Molecolari Agroalimentari, Facoltà di Agraria
Università di Milano, Via Celoria 2 20133, Milano, Italy
Received 7 February 2000; revised 8 May 2000; accepted 9 May 2000.;
Available online 25 March 2002.
Abstract
Prion diseases are characterized by the accumulation of altered forms of
the prion protein (termed PrPSc) in the brain. Unlike the normal protein,
PrPSc isoforms have a high content of β-sheet secondary structure, are
protease-resistant, and form insoluble aggregates and amyloid fibrils.
Evidence indicates that they are responsible for neuropathological
changes (i.e. nerve cell degeneration and glial cell activation) and
transmissibility of the disease process. Here, we show that the antibiotic
tetracycline: (i) binds to amyloid fibrils generated by synthetic peptides
corresponding to residues 106–126 and 82–146 of human PrP; (ii)
hinders assembly of these peptides into amyloid fibrils; (iii) reverts the
protease resistance of PrP peptide aggregates and PrPSc extracted from
brain tissue of patients with Creutzfeldt-Jakob disease; (iv) prevents
neuronal death and astrocyte proliferation induced by PrP peptides in
vitro. NMR spectroscopy revealed several through-space interactions
between aromatic protons of tetracycline and side-chain protons of
Ala117–119, Val121–122 and Leu125 of PrP 106–126. These properties
make tetracycline a prototype of compounds with the potential of
inactivating the pathogenic forms of PrP.
Author Keywords: amyloidogenesis; cell cultures; NMR spectroscopy;
PrP peptides; tetracycline
Abbreviations: BSE, bovine spongiform encephalopathy; CJD,
Creutzfeldt-Jakob disease; vCJD, new variant of Creutzfeldt-Jakob
disease; GSS, Gerstmann-Sträussler-Scheinker disease; PrP, prion
protein; PrPC, cellular isoform of PrP; PrPSc, scrapie isoform of PrP;
COSY-dQF, double quantum filtered correlated spectroscopy; TOCSY,
total correlated spectroscopy; NOE, nuclear Overhauser effect; NOESY,
NOE spectroscopy
Further Reading
H. Diringer and B. Ehlers, Chemoprophylaxis of scrapie in mice. J.
Gen. Virol. 72 (1991), pp. 457–460.
Corresponding author
1 Edited by J. Karn
Sun, September 17th, 2006. 09:27 am