> top > docs > PubMed:25239621 > annotations

PubMed:25239621 JSONTXT

Annnotations TAB JSON ListView MergeView

sentences

Id Subject Object Predicate Lexical cue
T1 0-141 Sentence denotes Alzheimer presenilin-1 mutations dramatically reduce trimming of long amyloid β-peptides (Aβ) by γ-secretase to increase 42-to-40-residue Aβ.
T2 142-353 Sentence denotes The presenilin-containing γ-secretase complex produces the amyloid β-peptide (Aβ) through intramembrane proteolysis, and >100 presenilin mutations are associated with familial early-onset Alzheimer disease (AD).
T3 354-473 Sentence denotes The question of whether these mutations result in AD through a gain or a loss of function remains highly controversial.
T4 474-628 Sentence denotes Mutations in presenilins increase ratios of 42- to 40-residue Aβ critical to pathogenesis, but other Aβs of 38-49 residues are also formed by γ-secretase.
T5 629-768 Sentence denotes Evidence in cells suggests the protease first cleaves substrate within the transmembrane domain at the ϵ site to form 48- or 49-residue Aβ.
T6 769-969 Sentence denotes Subsequent cleavage almost every three residues from the C terminus is thought to occur along two pathways toward shorter secreted forms of Aβ: Aβ49 → Aβ46 → Aβ43 → Aβ40 and Aβ48 → Aβ45 → Aβ42 → Aβ38.
T7 970-1325 Sentence denotes Here we show that the addition of synthetic long Aβ peptides (Aβ45-49) directly into purified preparations of γ-secretase leads to the formation of Aβ40 and Aβ42 whether the protease complex is detergent-solubilized or reconstituted into lipid vesicles, and the ratios of products Aβ42 to Aβ40 follow a pattern consistent with the dual-pathway hypothesis.
T8 1326-1480 Sentence denotes Kinetic analysis of five different AD-causing mutations in presenilin-1 revealed that all result in drastic reduction of normal carboxypeptidase function.
T9 1481-1737 Sentence denotes Altered trimming of long Aβ peptides to Aβ40 and Aβ42 by mutant proteases occurs at multiple levels, independent of the effects on initial endoproteolysis at the ϵ site, all conspiring to increase the critical Aβ42/Aβ40 ratio implicated in AD pathogenesis.
T10 1738-1881 Sentence denotes Taken together, these results suggest that specific reduction of carboxypeptidase function of γ-secretase leads to the gain of toxic Aβ42/Aβ40.

PubmedHPO

Id Subject Object Predicate Lexical cue
T1 201-208 HP_0011034 denotes amyloid
T2 330-347 HP_0002511 denotes Alzheimer disease

PubMed_ArguminSci

Id Subject Object Predicate Lexical cue
T1 142-145 DRI_Background denotes The
T2 180-353 DRI_Background denotes complex produces the amyloid β-peptide (Aβ) through intramembrane proteolysis, and >100 presenilin mutations are associated with familial early-onset Alzheimer disease (AD).
T3 354-473 DRI_Challenge denotes The question of whether these mutations result in AD through a gain or a loss of function remains highly controversial.
T4 474-628 DRI_Background denotes Mutations in presenilins increase ratios of 42- to 40-residue Aβ critical to pathogenesis, but other Aβs of 38-49 residues are also formed by γ-secretase.
T5 629-768 DRI_Background denotes Evidence in cells suggests the protease first cleaves substrate within the transmembrane domain at the ϵ site to form 48- or 49-residue Aβ.
T6 769-912 DRI_Approach denotes Subsequent cleavage almost every three residues from the C terminus is thought to occur along two pathways toward shorter secreted forms of Aβ:
T7 939-942 DRI_Approach denotes and
T8 968-969 DRI_Approach denotes .
T9 970-1325 DRI_Outcome denotes Here we show that the addition of synthetic long Aβ peptides (Aβ45-49) directly into purified preparations of γ-secretase leads to the formation of Aβ40 and Aβ42 whether the protease complex is detergent-solubilized or reconstituted into lipid vesicles, and the ratios of products Aβ42 to Aβ40 follow a pattern consistent with the dual-pathway hypothesis.
T10 1326-1480 DRI_Background denotes Kinetic analysis of five different AD-causing mutations in presenilin-1 revealed that all result in drastic reduction of normal carboxypeptidase function.
T11 1481-1737 DRI_Background denotes Altered trimming of long Aβ peptides to Aβ40 and Aβ42 by mutant proteases occurs at multiple levels, independent of the effects on initial endoproteolysis at the ϵ site, all conspiring to increase the critical Aβ42/Aβ40 ratio implicated in AD pathogenesis.
T12 1738-1881 DRI_Approach denotes Taken together, these results suggest that specific reduction of carboxypeptidase function of γ-secretase leads to the gain of toxic Aβ42/Aβ40.

mondo_disease

Id Subject Object Predicate Lexical cue mondo_id
T1 70-77 Disease denotes amyloid http://purl.obolibrary.org/obo/MONDO_0019065
T2 201-208 Disease denotes amyloid http://purl.obolibrary.org/obo/MONDO_0019065
T3 330-347 Disease denotes Alzheimer disease http://purl.obolibrary.org/obo/MONDO_0004975
T4 349-351 Disease denotes AD http://purl.obolibrary.org/obo/MONDO_0004975
T5 404-406 Disease denotes AD http://purl.obolibrary.org/obo/MONDO_0004975
T6 1361-1363 Disease denotes AD http://purl.obolibrary.org/obo/MONDO_0004975
T7 1721-1723 Disease denotes AD http://purl.obolibrary.org/obo/MONDO_0004975

HP-phenotype

Id Subject Object Predicate Lexical cue hp_id
T1 330-347 Phenotype denotes Alzheimer disease HP:0002511
T2 349-351 Phenotype denotes AD HP:0002511
T3 404-406 Phenotype denotes AD HP:0002511
T4 1361-1363 Phenotype denotes AD HP:0002511
T5 1721-1723 Phenotype denotes AD HP:0002511

Anatomy-UBERON

Id Subject Object Predicate Lexical cue uberon_id
T1 704-717 Body_part denotes transmembrane http://purl.obolibrary.org/obo/GO_0016020