Table 4.
Disease modifiers identified in Drosophila TDP-43-ALS models
| Disease modifier | Fly transgenic construct | Phenotypic rescue | Refs. |
|---|---|---|---|
| Phospholipase D pathway modulation | GMR-Gal4 > UAS-TDP-43M337V | Eye morphology | [91] |
|
Withania somnifera extracts |
D42-Gal4 > UAS-TBPHRNAi | Motor behavior, lifespan | [105] |
| Rapamycin | D42-Gal4 > UAS-TBPH | Motor behavior, lifespan | [174] |
|
ATG7 overexpression |
Act-Gal4 > TBPHΔ23/Δ23;UAS-Atg7 | Motor behavior, lifespan | [175] |
|
Mitofusin overexpression |
Elav-Gal4 > UAS-TDP-43;UAS-Marf | Motor behavior | [179] |
|
Parkin overexpression |
Elav-Gal4 > UAS-TDP-43;UAS-Parkin | Motor behavior, lifespan | [180] |
|
PINK-1 downregulation |
Elav-Gal4 > UAS-TDP-43;PINK1RNAi | Motor behavior, lifespan | |
|
Futsch overexpression |
D42-Gal4 > UAS-TDP-43;P(EP)futschEP1419 | Motor behavior, NMJ, lifespan | [181] |
|
Cacophony overexpression |
Elav-Gal4 > UAS-Cacophony;TBPHDD96 D42-Gal4 > UAS-Cacophony;TBPHDD96 |
Motor behavior | [183] |
|
6-(3-(4-fluorobenzyl)-3-(hydroxymethyl) piperidin-1-yl)pyrazine-2-carboxamide |
D42-Gal4 > UAS-TDP-43 | Motor behavior | [185] |
|
Drosophila REF1 downregulation |
GMR-Gal4 > UAS-TDP-43; UAS-ATXN2-32Q;UAS-Ref1RNAi |
Eye morphology | [186] |
| Medium-chain fatty acids | D42-Gal4 > UAS-TDP-43 | Motor behavior | [190] |
|
Palmitoyltransferase downregulation |
D42-Gal4 > UAS-TDP-43;Cpt1RNAi D42-Gal4 > UAS-TDP-43;Cpt2RNAi |
Motor behavior | |
|
Glycolysis upregulation |
D42-Gal4 > UAS-TDP-43;UAS-Glut3 D42-Gal4 > UAS-TDP-43;UAS-PFK |
Motor behavior | [191] |
|
Drosophila Atx2 downregulation |
GMR-Gal4 > dAtx2X1 Elav-Gal4 > dAtx2X1 |
Eye morphology, lifespan | [197] |
|
PABP2 downregulation |
GMR-Gal4 > UAS-TDP-43;PABP2LOF GMR-Gal4 > UAS-TDP-43 D169G;PABP2LOF GMR-Gal4 > UAS-TDP-43 A315T;PABP2LOF |
Eye morphology (worsening) | [201] |
|
D42-Gal4 > UAS-TDP-43;PABP2LOF D42-Gal4 > UAS-TDP-43 D169G;PABP2LOF D42-Gal4 > UAS-TDP-43 A315T;PABP2LOF |
Motor behavior (worsening) | ||
|
ATXN2 PAM2 domain depletion |
GMR-Gal4 > UAS-TDP-43;UAS-ATXN2-32QΔPAM2 ElavGS-Gal4 > UAS-TDP-43;UAS-ATXN2-32QΔPAM2 |
Eye morphology, motor behavior, lifespan | [199] |
|
Poly-ADP-ribose polymerase downregulation |
GMR-Gal4 > UAS-TDP-43;PARPRNAi Elav-Gal4 > UAS-TDP-43;PARPRNAi |
Eye morphology, motor behavior, lifespan | [203] |
|
Tankyrase downregulation |
GMR-Gal4 > UAS-TDP-43;TkrsIR Elav-Gal4 > UAS-TDP-43;TkrsIR |
Eye morphology, lifespan | [202] |