| 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. |
