Cerebrovascular P-glycoprotein expression is decreased in Creutzfeldt-Jakob disease

Acta Neuropathologica
Silke VogelgesangRolf W Warzok

Abstract

The abnormal conformation and assembly of proteins in the central nervous system is increasingly thought to be a critical pathogenic mechanism in neurodegenerative disorders such as Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease (AD). CJD is marked primarily by the buildup of misfolded prion protein (PrP(Sc)) in brain, whereas the accrual of beta-amyloid protein (Abeta) and tau protein are characteristic for AD. Prior studies have shown that the ATP-binding cassette transporter P-glycoprotein (P-gp) is a cellular efflux pump for Abeta, and that age-associated deficits in P-gp may be involved in the pathogenesis of Alzheimer's disease. In the present study, we investigated the relationship between P-gp and idiopathic CJD, and found that CJD, like AD, is associated with a decrease in the expression of cerebrovascular P-gp. In some instances, Abeta and PrP deposits coexist in cases of CJD, suggesting the possibility of pathogenic interactions. Since there is, to date, no evidence that PrP itself is a substrate for P-gp, we hypothesize that the age-related deficits in P-gp could promote the accumulation of PrP(Sc) either by promoting the buildup of Abeta (which could act as a seed for the aggregation of PrP(Sc)), or by ove...Continue Reading

References

Jul 12, 1997·Lancet·R W Carrell, D A Lomas
Apr 16, 1998·Alzheimer Disease and Associated Disorders·R W WarzokL C Walker
Jun 17, 1998·Proceedings of the National Academy of Sciences of the United States of America·M J SmythR W Johnstone
Aug 15, 1998·Acta Neuropathologica·J A HainfellnerH Budka
Nov 20, 1998·Trends in Genetics : TIG·A Kakizuka
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·E H KooJ W Kelly
Nov 14, 2000·The American Journal of Pathology·M F FrommD Schrenk
Feb 22, 2001·Journal of Neurochemistry·F C LamP B Reiner
Feb 7, 2002·Experimental Gerontology·Gábor G Kovács, Herbert Budka
Feb 19, 2002·British Journal of Clinical Pharmacology·Martina HennessyJ Feely
Jul 20, 2002·Lancet·Markus GlatzelAdriano Aguzzi
Oct 3, 2002·Annual Review of Pharmacology and Toxicology·Matthias SchwabMartin F Fromm
Oct 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·Fabrizio ChitiChristopher M Dobson
Jan 18, 2003·Vascular Pharmacology·Michel DemeuleRichard Béliveau
Jan 22, 2003·Advanced Drug Delivery Reviews·Alfred H Schinkel, Johan W Jonker
Apr 10, 2003·Experimental Neurology·M Lopez SalonE Soto
Aug 2, 2003·Annals of Neurology·Jens WiltfangMarkus Otto
Oct 3, 2003·British Medical Bulletin·Herbert Budka
Oct 10, 2003·Journal of Neuropathology and Experimental Neurology·Tamas ReveszJanice L Holton
Nov 1, 2003·Science·Adriano Aguzzi, Christian Haass
Jul 1, 2004·Annals of Medicine·Leonardo Petrucelli, Ted M Dawson
Jul 28, 2004·Trends in Pharmacological Sciences·Martin F Fromm
Nov 5, 2004·The EMBO Journal·Neena S RaneRamanujan S Hegde
Jan 13, 2005·Acta Neuropathologica·Ursula UnterbergerHerbert Budka
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·Tetsuya Terasaki, Sumio Ohtsuki
Oct 22, 2005·The Journal of Clinical Investigation·John R CirritoDavid M Holtzman

❮ Previous
Next ❯

Citations

Dec 4, 2009·PLoS Pathogens·Sina GhaemmaghamiStanley B Prusiner
Nov 17, 2009·Acta Neuropathologica·Casper JansenAnnemieke J M Rozemuller
Apr 20, 2010·Expert Opinion on Drug Metabolism & Toxicology·Caroline A LeeDennis A Smith
Aug 7, 2009·Journal of Neurochemistry·Magdalena von Wedel-ParlowHans-Joachim Galla
Jun 12, 2014·Revista brasileira de psiquiatria : orgão oficial da Associação Brasileira de Psiquiatria, Asociación Psiquiátrica de la América Latina·Carlos A Tovilla-ZárateBeatriz Camarena
Dec 17, 2020·Journal of Alzheimer's Disease : JAD·Amalia MerelliJerónimo Auzmendi
Apr 23, 2020·Pharmacology & Therapeutics·Eva Gil-MartinsRenata Silva

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Tau & TDP-43

Alzheimer's disease is a neurodegenerative disease. This feed focuses on the underlying role of tau proteins and TAR DNA-binding protein 43, as well as other genetic factors, in Alzheimer's disease.

Bovine Spongiform Encephalopathy

Bovine spongiform encephalopathy is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human Creutzfeldt-Jakob disease. Here is the latest research.

Bovine Spongiform Encephalopathy (MDS)

Bovine spongiform encephalopathy is a neurodegenerative disease belonging to the transmissible spongiform encephalopathies, a group of diseases including sheep scrapie and human Creutzfeldt-Jakob disease. Here is the latest research.