Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.21.64 (
proteinase K
)
4,071
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recently, a novel plaque-associated protein,
collagenous Alzheimer amyloid plaque component
(
CLAC
), was identified in brains from patients with Alzheimer's disease.
CLAC
is derived from a type II transmembrane collagen precursor protein, termed
CLAC-P
(collagen XXV). The biological function and the contribution of
CLAC
to the pathogenesis of Alzheimer's disease and plaque formation are unknown. In vitro studies indicate that
CLAC
binds to fibrillar, but not to monomeric, amyloid beta-peptide (Abeta). Here, we examined the effects of
CLAC
on Abeta fibrils using assays based on turbidity, thioflavin T binding, sedimentation analysis, and electron microscopy. The incubation of
CLAC
with preformed Abeta fibrils led to increased turbidity, indicating that larger aggregates were formed. In support of this contention, more Abeta was sedimented in the presence of
CLAC
, as determined by gel electrophoresis. Moreover, electron microscopy revealed an increased amount of Abeta fibril bundles in samples incubated with
CLAC
. Importantly, the frequently used thioflavin T-binding assay failed to reveal these effects of
CLAC
. Digestion with
proteinase K
or trypsin showed that Abeta fibrils, incubated together with
CLAC
, were more resistant to proteolytic degradation. Therefore,
CLAC
assembles Abeta fibrils into fibril bundles that have an increased resistance to proteases. We suggest that
CLAC
may act in a similar way in vivo.
...
PMID:Collagenous Alzheimer amyloid plaque component assembles amyloid fibrils into protease resistant aggregates. 1585 8
