| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-133 |
Sentence |
denotes |
Aggregation of the nucleic acid-binding protein TDP-43 occurs via distinct routes that are coordinated with stress granule formation. |
| T2 |
134-326 |
Sentence |
denotes |
TAR DNA-binding protein 43 (TDP-43) is a nucleic acid-binding protein, and its aggregation represents the defining pathology in amyotrophic lateral sclerosis (ALS) and related proteinopathies. |
| T3 |
327-433 |
Sentence |
denotes |
Recent studies implicate cytoplasmic stress granules (SGs) as hubs that may facilitate TDP-43 aggregation. |
| T4 |
434-582 |
Sentence |
denotes |
Here, using cellular fractionation, biochemical analyses, and histological assays, we show that TDP-43 targeted to the cytoplasm has multiple fates. |
| T5 |
583-820 |
Sentence |
denotes |
Whereas a TDP-43 subpopulation is indeed recruited to SGs, mature aggregated TDP-43, produced with aggregate-prone TDP-43 variants or exposure to oxidative stress, generates distinct TDP-43 inclusions that are surprisingly devoid of SGs. |
| T6 |
821-975 |
Sentence |
denotes |
Consistent with this observation, we found that SG components are predominantly excluded from TDP-43 pathology in motor neurons from individuals with ALS. |
| T7 |
976-1227 |
Sentence |
denotes |
We generated de novo SGs by expressing the fragile X protein (FMRP) and found that rather than directly engaging TDP-43 aggregates, SGs can sequester the proteostasis factor histone deacetylase 6 (HDAC6) and thereby impede TDP-43 clearance from cells. |
| T8 |
1228-1345 |
Sentence |
denotes |
These findings indicate that SGs form distinct cytoplasmic structures that can indirectly enhance TDP-43 aggregation. |
| T9 |
1346-1518 |
Sentence |
denotes |
Therapeutic approaches that inhibit SG formation may therefore be effective at suppressing TDP-43-mediated toxicity in patients with ALS and related TDP-43 proteinopathies. |
