| MLO | Phase separation |
|---|---|
| Class | LLPS |
| Synonyms | Phase transition, Liquid-liquid phase separation |
| Classification | nervous system disease |
|---|---|
| Disease | Frontotemporal dementia |
| More Disease Information | |
| MLO change | Size: - | Number: - | Assembly: - | ||
|---|---|---|---|---|---|
| Dynamic: - | Others: - | ||||
| Description: - | |||||
| Publication note | Downregulation of tankyrase,a poly(ADP-ribose) (PAR) polymerase,reduces TDP-43 accumulation in the cytoplasm and potently mitigates neurodegeneration. TDP-43 non-covalently binds to PAR via PAR-binding motifs embedded within its nuclear localization sequence. PAR binding promotes liquid-liquid phase separation of TDP-43 in vitro and is required for TDP-43 accumulation in stress granules in mammalian cells and neurons. Small-molecule inhibition of Tankyrase-1/2 in mammalian cells inhibits formation of cytoplasmic TDP-43 foci without affecting stress granule assembly.Tankyrase inhibition antagonizes TDP-43-associated pathology and neurodegeneration and could have therapeutic utility for ALS and FTD. | ||||
| Organism | Monkey,Drosophila | Cell line or tissue | Cos-7,Drosophila | ||
| Experiment evidence | Indirect experiment | Reference | 30045872,30100264 | ||
| In vivo PS evidence | FRAP: Yes | 1,6-hexa treatment: Yes | Spherical shape: Yes | ||
| Fusion&Fission: No | PS role: Scaffold | ||||
| Mutation | - | Expression change | - |
|---|---|---|---|
| PTM | Position Residue | Modification | Modifying enzyme |
| - | - | - | |
| Description | Mutation: - Expression change: - PTM: Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization |
||
| Drugs from DrugBank | - | |
|---|---|---|
| Molecules from BindingDB(PubChem CID) | 45223816；121380360；56739767；863；4212；6112 | |
| Molecules from PDBBind | - | |
| Interference Note | - |
| Pscore overall score | 5.95 | PSPer | 0.38 |
|---|---|---|---|
| catGRANULE overall score | 2.04 | R+Y | 0.0018461538000000002 |
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Chao Hou, Haotai Xie, Yang Fu, Yao Ma, Tingting Li. MloDisDB: A manually curated DataBase of the relations between MembraneLess Organelles and DISeases