Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-149 |
DRI_Background |
denotes |
Disrupted autophagy leads to dopaminergic axon and dendrite degeneration and promotes presynaptic accumulation of α-synuclein and LRRK2 in the brain. |
T2 |
150-374 |
DRI_Background |
denotes |
Parkinson's disease (PD) is characterized pathologically by the formation of ubiquitin and α-synuclein (α-syn)-containing inclusions (Lewy bodies), dystrophic dopamine (DA) terminals, and degeneration of midbrain DA neurons. |
T3 |
375-462 |
DRI_Challenge |
denotes |
The precise molecular mechanisms underlying these pathological features remain elusive. |
T4 |
463-660 |
DRI_Challenge |
denotes |
Accumulating evidence has implicated dysfunctional autophagy, the cell self-digestion and neuroprotective pathway, as one of the pathogenic systems contributing to the development of idiopathic PD. |
T5 |
661-832 |
DRI_Outcome |
denotes |
Here we characterize autophagy-deficient mouse models and provide in vivo evidence for the potential role that impaired autophagy plays in pathogenesis associated with PD. |
T6 |
833-991 |
DRI_Challenge |
denotes |
Cell-specific deletion of essential autophagy gene Atg7 in midbrain DA neurons causes delayed neurodegeneration, accompanied by late-onset locomotor deficits. |
T7 |
992-1210 |
DRI_Background |
denotes |
In contrast, Atg7-deficient DA neurons in the midbrain exhibit early dendritic and axonal dystrophy, reduced striatal dopamine content, and the formation of somatic and dendritic ubiquitinated inclusions in DA neurons. |
T8 |
1211-1394 |
DRI_Background |
denotes |
Furthermore, whole-brain-specific loss of Atg7 leads to presynaptic accumulation of α-syn and LRRK2 proteins, which are encoded by two autosomal dominantly inherited PD-related genes. |
T9 |
1395-1526 |
DRI_Outcome |
denotes |
Our results suggest that disrupted autophagy may be associated with enhanced levels of endogenous α-syn and LRRK2 proteins in vivo. |
T10 |
1527-1662 |
DRI_Challenge |
denotes |
Our findings implicate dysfunctional autophagy as one of the failing cellular mechanisms involved in the pathogenesis of idiopathic PD. |