| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
94-262 |
DRI_Approach |
denotes |
The G2019S mutation in the multidomain protein leucine-rich repeat kinase 2 (LRRK2) is one of the most frequently identified genetic causes of Parkinson's disease (PD). |
| T2 |
263-455 |
DRI_Challenge |
denotes |
Clinically, LRRK2(G2019S) carriers with PD and idiopathic PD patients have a very similar disease with brainstem and cortical Lewy pathology (α-synucleinopathy) as histopathological hallmarks. |
| T3 |
456-489 |
DRI_Background |
denotes |
Some patients have Tau pathology. |
| T4 |
490-643 |
DRI_Background |
denotes |
Enhanced kinase function of the LRRK2(G2019S) mutant protein is a prime suspect mechanism for carriers to develop PD but observations in LRRK2 knock-out, |
| T5 |
660-775 |
DRI_Background |
denotes |
and kinase-dead mutant mice suggest that LRRK2 steady-state abundance of the protein also plays a determining role. |
| T6 |
776-918 |
DRI_Background |
denotes |
One critical question concerning the molecular pathogenesis in LRRK2(G2019S) PD patients is whether α-synuclein (aSN) has a contributory role. |
| T7 |
919-1046 |
DRI_Outcome |
denotes |
To this end we generated mice with high expression of either wildtype or G2019S mutant LRRK2 in brainstem and cortical neurons. |
| T8 |
1262-1394 |
DRI_Outcome |
denotes |
On the contrary, in some lines high LRRK2 levels improved motor skills in the presence and absence of aSN-transgene-induced disease. |
| T9 |
1395-1528 |
DRI_Challenge |
denotes |
Therefore, in many neurons high LRRK2 levels are well tolerated and not sufficient to drive or exacerbate neuronal α-synucleinopathy. |
