Browse by author
Lookup NU author(s): Professor Colin Dingwall
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
The serine protease plasmin can efficiently degrade amyloid peptide in vitro, and is found at low levels in the hippocampus of patients with Alzheimer's disease (AD). The cause of such paucity remains unknown. We show here that the levels of total brain plasminogen and plasminogen-binding molecules are normal in these brain samples, yet plasminogen membrane binding is greatly reduced. Biochemical analysis reveals that the membranes of these brains have a mild, still significant, cholesterol reduction compared to age-matched controls, and anomalous raft microdomains. This was reflected by the loss of raft-enriched proteins, including plasminogen-binding and -activating molecules. Using hippocampal neurons in culture, we demonstrate that removal of a similar amount of membrane cholesterol is sufficient to induce raft disorganization, leading to reduced plasminogen membrane binding and low plasmin activity. These results suggest that brain raft alterations may contribute to AD by rendering the plasminogen system inefficient.
Author(s): Ledesma MD, Abad-Rodriguez J, Galvan C, Biondi E, Navarro P, Delacourte A, Dingwall C, Dotti CG
Publication type: Article
Publication status: Published
Journal: EMBO Reports
Year: 2003
Volume: 4
Issue: 12
Pages: 1190-1196
ISSN (print): 1469-221X
ISSN (electronic): 1469-3178
Publisher: Nature Publishing Group
URL: http://dx.doi.org/10.1038/sj.embor.7400021
DOI: 10.1038/sj.embor.7400021
Altmetrics provided by Altmetric
