近期,EMBO J.上发表了题为“Loss of TDP-43 oligomerization or RNA binding elicits distinct aggregation patterns”的文章,揭示了寡聚和RNA结合控制着TDP-43的稳定性、剪接功能、LLPS和亚细胞定位。作者着重提出,TDP-43的寡聚是由RNA...
Protein aggregation plays key roles in age-related degenerative diseases, but how different proteins coalesce to form inclusions that vary in composition, morphology, molecular dynamics and confer physiological consequences is poorly understood. Here we
2. B. S. Johnson et al., TDP-43 is intrinsically aggregation-prone, and amyotrophic lateral sclerosis-linked mutations accelerate aggregation and increase toxicity. J. Biol. Chem. 284, 20329–20339 (2009). doi: 10.1074/jbc.M109.010264;pmid: 19465477 3. T. Arai et al., TDP-43 is a com...
The agent for prevention or treatment of neurodegenerative diseases induced by abnormal accumulation of TDP-43 in cells comprises such nucleic acid as an active ingredient.YOKOTA TakanoriSAKAUE Fumika
8.Liu, R., et al., Reducing TDP-43 aggregation does not prevent its cytotoxicity. Acta Neuropathologica Communications, 2013. 1(1): p. 1-11. 9.Gao, N., et al., TDP-43 specific reduction induced by Di-hyd...
We have investigated the role of metabolic stress in protein aggregate formation analyzing how it is relevant to the co-aggregation observed between RGNEF and TDP-43 in motor neurons of ALS patients. Metabolic stress was able to induce formation of micronuclei, small nuclear fragments, in cultured...
We review the relationship of stress granules and TDP-43 pathological aggregation. We propose two possible models for TDP-43 aggregate formation. In one model, TDP-43 aggregation is "independent" of stress granule formation. In another model, stress granules are "precursors" to TDP-43 aggregation...
[3] DiFiglia M, Sapp E, Chase K O, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain[J]. Science, 1997, 277(5334): 1990-1993. [4] Scherzinger E, Lurz R, Turmaine M, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like...
[3] DiFiglia M, Sapp E, Chase K O, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain[J]. Science, 1997, 277(5334): 1990-1993. [4] Scherzinger E, Lurz R, Turmaine M, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like...
We found that two of the synthetic peptides identified with this approach could effectively inhibit the formation of TDP-43 protein aggregates in a concentration-dependent manner in HeLa cells in which a mutated human TDP-43 gene was overexpressed. However, despite reducing aggregation, these ...