| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-98 |
Sentence |
denotes |
Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with Lewy bodies. |
| T2 |
99-256 |
Sentence |
denotes |
Two missense mutations (P123H and V70M) of beta-synuclein (beta-syn), the homologue of alpha-syn, have been recently identified in dementia with Lewy bodies. |
| T3 |
257-377 |
Sentence |
denotes |
However, the mechanism through which these mutations influence the pathogenesis of dementia with Lewy bodies is unclear. |
| T4 |
378-515 |
Sentence |
denotes |
To investigate the role of the beta-syn mutations in neurodegeneration, each mutant was stably transfected into B103 neuroblastoma cells. |
| T5 |
516-804 |
Sentence |
denotes |
Cells overexpressing mutated beta-syn had eosinophilic cytoplasmic inclusion bodies immunopositive for mutant beta-syn, and electron microscopy revealed that these cells were abundant in various cytoplasmic membranous inclusions resembling the histopathology of lysosomal storage disease. |
| T6 |
805-1002 |
Sentence |
denotes |
Consistent with these findings, the inclusion bodies were immunopositive for lysosomal markers, including cathepsin B, LAMP-2, GM2 ganglioside, and ATP13A2, which has recently been linked to PARK9. |
| T7 |
1003-1258 |
Sentence |
denotes |
Notably, formation of these lysosomal inclusions was greatly stimulated by co-expression of alpha-syn, was dependent on the phosphorylation of alpha-syn at Ser-129, and was more efficient with the A53T familial mutant of alpha-syn compared with wild type. |
| T8 |
1259-1602 |
Sentence |
denotes |
Furthermore, the inclusion formation in cells overexpressing mutant beta-syn and transfected with alpha-syn was significantly suppressed by treatment with autophagy-lysosomal inhibitors, which were associated with impaired clearance of syn proteins and enhanced apoptosis, indicating that formation of lysosomal inclusions might be protective. |
| T9 |
1603-1779 |
Sentence |
denotes |
Collectively, the results demonstrated unambiguously that overexpression of beta-syn mutants (P123H and V70M) in neuroblastoma cells results in an enhanced lysosomal pathology. |
| T10 |
1780-1894 |
Sentence |
denotes |
We suggest that these missense mutations of beta-syn might play a causative role in stimulating neurodegeneration. |
