PubMed_ArguminSci  

PubMed:28127059 JSONTXT 15 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T1 145-184 DRI_Background denotes Autosomal-dominant adult-onset neuronal
T2 207-301 DRI_Background denotes (ANCL) is caused by mutation of the DNAJC5 gene encoding cysteine string protein alpha (CSPα).
T3 302-616 DRI_Challenge denotes The disease-causing mutations, which result in substitution of leucine-115 with an arginine (L115R) or deletion of the neighbouring leucine-116 (∆L116) in the cysteine-string domain cause CSPα to form high molecular weight SDS-resistant aggregates, which are also present in post-mortem brain tissue from patients.
T4 617-818 DRI_Background denotes Formation and stability of these mutant aggregates is linked to palmitoylation of the cysteine-string domain, however the regions of the mutant proteins that drive aggregation have not been determined.
T5 819-991 DRI_Background denotes The importance of specific residues in the cysteine-string domain was investigated, revealing that a central core of palmitoylated cysteines is essential for aggregation of
T6 1002-1010 DRI_Background denotes mutants.
T7 1011-1051 DRI_Outcome denotes Interestingly, palmitoylated monomers of
T8 1062-1294 DRI_Outcome denotes mutants were shown to be short-lived compared with wild-type CSPα, suggesting that the mutants either have a faster rate of depalmitoylation or that they are consumed in a time-dependent manner into high molecular weight aggregates.
T9 1295-1507 DRI_Background denotes These findings provide new insight into the features of CSPα that promote aggregation in the presence of L115R/∆L116 mutations and reveal a change in the lifetime of palmitoylated monomers of the mutant proteins.