Table 1.

Changes in levels of WNT signaling components in human ALS- and SOD1–G93A transgenic mouse and motor neuron.

Methods	Research Subject		Inhibitor and Antagonist	WNT Ligands	Receptors	Downstream Molecules
Gene Expression Profiling PCR Array	SOD1–G93A transgenic mouse spinal cords [27]	95 d		↑ Wnt1, Wnt3a, Wnt7b, Wnt8a	↑ Fzd3	↑ Fosl1, Frat1 ↓ Myc, T, Tcf7
		108 d	↑ Wif1 and sFrp4	↑ Wnt4 ↓ Wnt16, Wnt8b		↑ Fgf4, Fosl1, Sfrp4, ↓ Csnk1a1, Frat1, FrzbLef1, Nkd1, Pitx2, Sfrp1, T, Tle2
		122 d		↑ Wnt10a, Wnt11, Wnt16, Wnt2, Wnt3, Wnt4, Wnt5a, Wnt5b, Wnt7a, Wnt7b, Wnt9a	↑ Fzd1, Fzd2, Fzd3, Fzd4, Fzd5, Fzd6, Fzd7, Fzd8, Lrp5	↑ Btrc, Ccnd1/2/3, Csnk1a–1, Ctnnb1, Dvl1, Ep300, Fbxw4/11, Fosl1, Frzb, Jun, Myc, Nlk, Pitx2, Ppp2r5d, Rhou, Senp2, Sfrp4, Slc9a3r1, Sox17, T, Tcf3, Wif1 ↓ Tcf7
Gene Expression Profiling PCR Array	ALS human spinal cords [37]		↑ sFRP3	↑ WNT3, WNT4, WNT2B, WNT5A	↑ FZD2, and FZD8, FZD3, LRP5,
Gene Expression Profiling PCR Array	SOD1–G93A transgenic mouse Skeletal Muscle [43]	40 d				↑ Prkx, Dner
		80 d			↓ Fzd2	↓ Cd44
RNA sequencing	SOD1 mutant motor neurons(iPSC) [44]				↑ Fzd2	↑ Lef, Tcf7l2 β–catenin
RNA sequencing	hSOD1–G93A mutant motor neurons (NSC34 cell) [45]					↑ Cltc, Plcb3, Plec, Psmd3, Ruvbl1
Immunofluorescence, Western blot, RT–PCR	astrocytes in SOD1–G93A transgenic mouse spinal cords			↑ WNT2A, WNT7A [30] WNT3A [29] WNT5A [28]	↑ FZD2 [28]	↑ nuclear β–catenin [29]
Immunofluorescence	astrocytes in ALS human spinal cords [37]			↑ WNT5A	↑ FZD2
Immunofluorescence, Western blot, RT–PCR	neurons in SOD1–G93A transgenic mouse spinal cords			↓ WNT3A [29] WNT5A [28]	↑ FZD5 [40]	↑ nuclear β–catenin, Phospho–GSK–3β (Ser 9) [29]
Immunofluorescence	hSOD1–G93A mutant motor neurons (NSC34 cell) [34]					↑ cytoplasm β–catenin
RNA sequencing, Western blot	Skeletal muscle and the neuromuscular junction in ALS human and SOD1–G93A mouse [46]		↑ FRZB			↑ β–catenin
Immunofluorescence [47]	limb muscles in ALS human			↓ WNT1, WNT3A, WNT7A		↑ β–catenin
	myofiber in ALS human			↑ WNT7A ↓ WNT1, WNT3A,
	neuromuscular junctions in SOD1–G93A mouse			↓ WNT1, WNT3A, WNT5A WNT7A
	extraocular muscles in ALS human and SOD1–G93A mouse					↑ β–catenin
cell–based assay and radio– immunoassay	sera from sporadic ALS patients [48,49]				↑ LRP4

↑: increase, ↓: decrease; Btrc, Beta–transducin repeat containing protein; Ccnd1/2/3, Cyclin D1/2/3; snk1a1, Casein kinase 1, alpha 1; Ctnnb1, Catenin (cadherin associated protein), beta 1; Dner, Delta Notch ligand/receptor; Dvl1, Dishevelled, dsh homolog 1 (Drosophila); Ep300,E1A binding protein p300; Fbxw4/11, F–box and WD–40 domain protein 11; Fgf4, Fibroblast growth factor 4; Fosl1, Fos–like antigen 1; Frat1, Frequently rearranged in advanced T–cell; Frzb, Frizzled–related protein; FRZB, Frizzled Related Protein; Jun, Jun oncogene; Lef1, Ly–phoid enhancer binding factor 1; Myc, Myelocytomatosis oncogene; Nkd1, Naked cuticle 1 homolog (Drosophila); Nlk, Nemo like kinase; Pitx2, Paired–like homeodomain transcription factor 2; Prkx, protein kinase X gene; Ppp2r5d, Protein phosphatase 2, regulatory subunit B (B56), delta isoform; iPSC, induced pluripotent stem cells; Rhou, Ras homolog gene family, member U; Senp2, SUMO/sentrin specific peptidase 2; sFRP13//4, Secreted frizzled–related protein 4; Slc9a3r1, Solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1; Sox17, SRY–box containing gene 17; RUVBL1, RuvB Like AAA ATPase 1; T, Brachyury; Tcf3/7, Transcription factor 7; Tle2, Transducin–like enhancer of split 2; Wif1, WNT inhibitory factor 1.