PMID- 10526337
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20201209
IS  - 1097-6256 (Print)
IS  - 1097-6256 (Linking)
VI  - 2
IP  - 11
DP  - 1999 Nov
TI  - Furin mediates enhanced production of fibrillogenic ABri peptides in familial
      British dementia.
PG  - 984-8
AB  - 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.
FAU - Kim, S H
AU  - Kim SH
AD  - Department of Neurobiology, Pharmacology and Physiology, The University of
      Chicago, Abbott 316, 947 East 58th Street, Chicago, Illinois 60637, USA.
FAU - Wang, R
AU  - Wang R
FAU - Gordon, D J
AU  - Gordon DJ
FAU - Bass, J
AU  - Bass J
FAU - Steiner, D F
AU  - Steiner DF
FAU - Lynn, D G
AU  - Lynn DG
FAU - Thinakaran, G
AU  - Thinakaran G
FAU - Meredith, S C
AU  - Meredith SC
FAU - Sisodia, S S
AU  - Sisodia SS
LA  - eng
GR  - 5 T32 GM07281/GM/NIGMS NIH HHS/United States
GR  - AG14248/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Neurosci
JT  - Nature neuroscience
JID - 9809671
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amyloid)
RN  - 0 (ITM2B protein, human)
RN  - 0 (Itm2b protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Peptide Fragments)
RN  - EC 3.4.21.- (Subtilisins)
RN  - EC 3.4.21.75 (Furin)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amyloid/*biosynthesis
MH  - Animals
MH  - Dementia/*genetics
MH  - Furin
MH  - Heredodegenerative Disorders, Nervous System/*genetics/metabolism
MH  - Membrane Glycoproteins
MH  - Membrane Proteins
MH  - Mice
MH  - Microscopy, Electron
MH  - Neurofibrils/*metabolism
MH  - Peptide Fragments/*biosynthesis
MH  - Subtilisins/*physiology
MH  - Tumor Cells, Cultured
MH  - United Kingdom
EDAT- 1999/10/20 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/10/20 09:00
PHST- 1999/10/20 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/10/20 09:00 [entrez]
AID - 10.1038/14783 [doi]
PST - ppublish
SO  - Nat Neurosci. 1999 Nov;2(11):984-8. doi: 10.1038/14783.