| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-122 |
Sentence |
denotes |
Neuronatin-mediated aberrant calcium signaling and endoplasmic reticulum stress underlie neuropathology in Lafora disease. |
| T2 |
123-368 |
Sentence |
denotes |
Lafora disease (LD) is a teenage-onset inherited progressive myoclonus epilepsy characterized by the accumulations of intracellular inclusions called Lafora bodies and caused by mutations in protein phosphatase laforin or ubiquitin ligase malin. |
| T3 |
369-474 |
Sentence |
denotes |
But how the loss of function of either laforin or malin causes disease pathogenesis is poorly understood. |
| T4 |
475-575 |
Sentence |
denotes |
Recently, neuronatin was identified as a novel substrate of malin that regulates glycogen synthesis. |
| T5 |
576-739 |
Sentence |
denotes |
Here we demonstrate that the level of neuronatin is significantly up-regulated in the skin biopsy sample of LD patients having mutations in both malin and laforin. |
| T6 |
740-858 |
Sentence |
denotes |
Neuronatin is highly expressed in human fetal brain with gradual decrease in expression in developing and adult brain. |
| T7 |
859-1002 |
Sentence |
denotes |
However, in adult brain, neuronatin is predominantly expressed in parvalbumin-positive GABAergic interneurons and localized in their processes. |
| T8 |
1003-1210 |
Sentence |
denotes |
The level of neuronatin is increased and accumulated as insoluble aggregates in the cortical area of LD brain biopsy samples, and there is also a dramatic loss of parvalbumin-positive GABAergic interneurons. |
| T9 |
1211-1423 |
Sentence |
denotes |
Ectopic expression of neuronatin in cultured neuronal cells results in increased intracellular Ca(2+), endoplasmic reticulum stress, proteasomal dysfunction, and cell death that can be partially rescued by malin. |
| T10 |
1424-1565 |
Sentence |
denotes |
These findings suggest that the neuronatin-induced aberrant Ca(2+) signaling and endoplasmic reticulum stress might underlie LD pathogenesis. |
