http://www.ncbi.nlm.nih.gov/pubmed/15661498
Koska D-penisillamiin voi estää kollageenin poikkisidosten muodostusta, sillä voisi olla merkitystä myös kelaattina Alz- taudissa estämässä hankalia fibrillimuodostumia. Löytyyhän tästä artikkelikin:
Eur J Pharm Biopharm. 2005 Feb;59(2):263-72. Novel D-penicillamine carrying nanoparticles for metal chelation therapy in Alzheimer's and other CNS diseases.
Koska D-penisillamiin voi estää kollageenin poikkisidosten muodostusta, sillä voisi olla merkitystä myös kelaattina Alz- taudissa estämässä hankalia fibrillimuodostumia. Löytyyhän tästä artikkelikin:
Eur J Pharm Biopharm. 2005 Feb;59(2):263-72. Novel D-penicillamine carrying nanoparticles for metal chelation therapy in Alzheimer's and other CNS diseases.
Source
Department of Pharmaceutical Sciences, Center for Pharmaceutical Science and Technology, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.Abstract
Metal ions accumulate in the brain with aging and in several neurodegenerative diseases. Aside from the copper storage disease, Wilson's disease, recent attention has focused on the accumulation of zinc, copper and iron in the Alzheimer's disease (AD) brain and the accumulation of iron in Parkinson's disease.
In particular, the parenchymal deposition of beta-amyloid (Abeta) and
its interaction with metal ions has been postulated to play a role in
the progression of AD. Thus, the strategy of lowering brain metal ions
and targeting the interaction of Abeta peptide and metal ions through
the administration of chelators has merit. Our recent finding that
nanoparticle delivery systems can cross the blood-brain barrier has led
us to investigate whether chelators delivered conjugated to
nanoparticles could act to reverse metal ion induced protein
precipitation. In the present studies, the Cu (I) chelator D-penicillamine
was covalently conjugated to nanoparticles via a disulfide bond or a
thioether bond. Nanoparticle-chelator conjugates were stable between pH
6-8 in aqueous suspension if stored at 4 degrees C, and did not
aggregate when challenged with salts and serum. Release of D-penicillamine
from the nanoparticles was achieved using reducing agents such as
dithiothreitol (as a model for glutathione). Nanoparticles treated only
under reducing conditions that released the conjugated D-penicillamine
were able to effectively resolubilize copper-Abeta (1-42) aggregates.
These results indicate that nanoparticles have potential to deliver D-penicillamine
to the brain for the prevention of Abeta (1-42) accumulation, as well
as to reduce metal ion accumulation in other CNS diseases.
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