Journal article
Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia
Nature neuroscience, Vol.2(11), pp.984-988
11/1999
DOI: 10.1038/14783
PMID: 10526337
Abstract
The genetic lesion underlying familial British dementia (FBD), an autosomal dominant neurodegenerative disorder, is a T-A transversion at the termination codon of the BRI gene. The mutant gene encodes BRI-L, the precursor of ABri peptides that accumulate in amyloid deposits in FBD brain. We now report that both BRI-L and its wild-type counterpart, BRI, were constitutively processed by the proprotein convertase, furin, resulting in the secretion of carboxyl-terminal peptides that encompass all or part of ABri. Elevated levels of peptides were generated from the mutant BRI precursor. Electron microscopic studies revealed that synthetic ABri peptides assembled into irregular, short fibrils. Collectively, our results support the view that enhanced furin-mediated processing of mutant BRI generates fibrillogenic peptides that initiate the pathogenesis of FBD.
Details
- Title: Subtitle
- Furin mediates enhanced production of fibrillogenic ABri peptides in familial British dementia
- Creators
- Donald F Steiner - Howard Hughes Medical Institute, The University of Chicago, Abbott 316Gopal Thinakaran - Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Abbott 316Stephen C Meredith - Department of Pathology, The University of Chicago, Abbott 316Rong Wang - Laboratory of Mass Spectrometry, Rockefeller UniversityJoseph Bass - Howard Hughes Medical Institute, The University of Chicago, Abbott 316Seong-Hun Kim - Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Abbott 316David J Gordon - Medical Scientists Training Program and Department of Biochemistry and Molecular Biology, The University of Chicago, Abbott 316Sangram S Sisodia - Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Abbott 316David G Lynn - Department of Chemistry, The University of Chicago, Abbott 316
- Resource Type
- Journal article
- Publication Details
- Nature neuroscience, Vol.2(11), pp.984-988
- DOI
- 10.1038/14783
- PMID
- 10526337
- ISSN
- 1097-6256
- eISSN
- 1546-1726
- Language
- English
- Date published
- 11/1999
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984093485602771
Metrics
9 Record Views