Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
97-333 |
DRI_Challenge |
denotes |
Neuritic retraction represents a prominent feature of the degenerative phenotype associated with mutations in leucine rich repeat kinase 2 (LRRK2) that are implicated in autosomal dominant and some cases of sporadic Parkinson's disease. |
T2 |
334-461 |
DRI_Background |
denotes |
Alterations in macroautophagy, the vacuolar catabolism of cytoplasmic constituents, have been described in Parkinson's disease. |
T3 |
462-623 |
DRI_Approach |
denotes |
In this study, we utilized retinoic-acid differentiated SH-SY5Y cells to determine whether autophagy contributes to mutant LRRK2-associated neurite degeneration. |
T4 |
624-639 |
DRI_Background |
denotes |
Transfection of |
T5 |
667-852 |
DRI_Background |
denotes |
cells with LRRK2 cDNA containing the common G2019S mutation resulted in significant decreases in neurite length, which were not observed in cells transfected with wild type LRRK2 or its |
T6 |
872-881 |
DRI_Background |
denotes |
mutation. |
T7 |
882-888 |
REPLACED |
denotes |
G2019S |
T8 |
895-1213 |
DRI_Outcome |
denotes |
transfected cells also exhibited striking increases in autophagic vacuoles in both neuritic and somatic compartments, as demonstrated by fluorescence and western blot analysis of the autophagy marker green fluorescent protein-tagged microtubule-associated protein Light Chain 3 and by transmission electron microscopy. |
T9 |
1214-1343 |
DRI_Background |
denotes |
RNA interference knockdown of LC3 or Atg7, two essential components of the conserved autophagy machinery, reversed the effects of |
T10 |
1357-1440 |
DRI_Background |
denotes |
expression on neuronal process length, whereas rapamycin potentiated these effects. |
T11 |
1441-1633 |
DRI_Background |
denotes |
The mitogen activated protein kinase/extracellular signal regulated protein kinase (MAPK/ERK) kinase (MEK) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126) reduced |
T12 |
1657-1730 |
DRI_Background |
denotes |
autophagy and neurite shortening, implicating MAPK/ERK-related signaling. |
T13 |
1731-1845 |
DRI_Background |
denotes |
These results indicate an active role for autophagy in neurite remodeling induced by pathogenic mutation of LRRK2. |