PubMed_ArguminSci  

PubMed:25905915 JSONTXT 10 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 128-230 DRI_Approach denotes Cysteine string protein (CSPα) is a presynaptic J protein co-chaperone that opposes neurodegeneration.
T2 231-330 DRI_Background denotes Mutations in CSPα (i.e., Leu115 to Arg substitution or deletion (Δ) of Leu116) cause adult neuronal
T3 353-410 DRI_Background denotes (ANCL), a dominantly inherited neurodegenerative disease.
T4 411-605 DRI_Outcome denotes We have previously demonstrated that CSPα limits the expression of large conductance, calcium-activated K+ (BK) channels in neurons, which may impact synaptic excitability and neurotransmission.
T5 606-773 DRI_Outcome denotes Here we show by western blot analysis that expression of the pore-forming BKα subunit is elevated ~2.5 fold in the post-mortem cortex of a 36-year-old patient with the
T6 787-796 DRI_Outcome denotes mutation.
T7 797-934 DRI_Outcome denotes Moreover, we find that the increase in BKα subunit level is selective for ANCL and not a general feature of neurodegenerative conditions.
T8 935-1128 DRI_Background denotes While reduced levels of CSPα are found in some postmortem cortex specimens from Alzheimer's disease patients, we find no concomitant increase in BKα subunit expression in Alzheimer's specimens.
T9 1129-1247 DRI_Approach denotes Both CSPα monomer and oligomer expression are reduced in synaptosomes prepared from ANCL cortex compared with control.
T10 1248-1314 DRI_Background denotes In a cultured neuronal cell model, CSPα oligomers are short lived.
T11 1315-1551 DRI_Outcome denotes The results of this study indicate that the Leu116∆ mutation leads to elevated BKα subunit levels in human cortex and extend our initial work in rodent models demonstrating the modulation of BKα subunit levels by the same CSPα mutation.
T12 1552-1731 DRI_Challenge denotes While the precise sequence of pathogenic events still remains to be elucidated, our findings suggest that dysregulation of BK channels may contribute to neurodegeneration in ANCL.