Table 1.

Summary of the studies and main findings described in the literature for Wnt-related molecules alterations in ALS

Species	Model	Wnt-related molecule/signaling alterations
		mRNA levels in ALS	Protein levels in ALS	Cellular expression pattern
				WT	ALS	Reference
Mouse	SOD1G93A	↑ Wnt1, Wnt2, Wnt3, Wnt3a, Wnt4, Wnt5a, Wnt5b, Wnt7a, Wnt7b, Wnt8a, Wnt9a, Wnt10a, Wnt11, Wnt16, Fz1, Fz2, Fz3, Fz4, Fz5, Fz6, Fz7, Fz8, Fz9, Fz10, LRP5, Wif1, sFRP3 and sFRP4. ↓ Wnt8b, Wnt16, sFRP1 and sFRP3.	↑ Wnt4 ↑ Wif1	Neurons and astrocytes Neurons and astrocytes	↑ Astrocytes ↓ Neurons ↑ Astrocytes ↓ Neurons	Yu et al., 2013
Mouse	SOD1G93A	↑ Wnt5a, Wnt7b, Fz1, Fz2, Fz3, Fz8, ROR2 and Wif1 ↓ Wnt4 and Fz4	Fz5 NE	Neurons and astrocytes	↑ Neurons	Gonzalez-Fernandez et al., 2016b
Mouse	SOD1G93A	↑ Wnt2 and Wnt7a = GSK-3β	↑ Wnt2. ↑ Wnt7a ↑ P-GSK-3β	Neurons and astrocytes Neurons and astrocytes Neurons	↑ Astrocytes ↑ Astrocytes =	Chen et al., 2012b
Mouse	SOD1G93A	↑ Wnt5a and Fz2	↑ Wnt5a ↑ Fz2	Neurons and astrocytes Neurons and astrocytes	↑ Astrocytes ↓ Neurons ↑ Astrocytes ↓ Neurons	Li et al., 2013
	Primary cultured astrocytes	NE	↑ Wnt5a ↑ Fz2
	NSC34-hSOD1 mutated cells	NE	↓ Wnt5a ↓ Fz2
Mouse	SOD1G93A	↑ Wnt1 and Fz1	↑ Wnt1 ↓ Fz1	Neurons and astrocytes Neurons and astrocytes	↑ Astrocytes ↑ Astrocytes	Wang et al., 2013
	Primary cultured astrocytes	NE	↑ Wnt1
	N2a-hSOD1 mutated cells	NE	↓ Wnt1
Mouse	SOD1G93A	↑ Wnt3a and Cyclin D1	↑ Wnt3a	Neurons and astrocytes	↑ Astrocytes ↓ Neurons	Chen et al., 2012a
		=β-caterin	=β-caterin	Neurons and astrocytes	↑ Astrocytes ↓ Neurons
			↑ Nuclear β-catenin
			↑ Cyclin D1	Neurons and astrocytes	↑ Astrocytes
Mouse	SOD1G93A	NE	↑ aPKC.	Neurons and oligodendrocytes	↑ Astrocytes	Tury et al., 2014
			Ryk NE	Neurons and oligodendrocytes	↑ MNs ↑ Axons
Mouse	NSC34-hSOD1 mutated cells	NE	↑β-catenin cytosolic aggregates			Pinto et al., 2013; Pinto et al., 2019
Human	MNs differentiated from iPSCs derived from ALS patients	ND	↑ Nuclear β-catenin			Bhinge et al., 2017
Human	ALS patients	NE	Wnt1 NE Wnt3a NE	Axons Axons	↑ Axons in EOM compared to LM ↑ Axons in EOM compared to LM	McLoon et al., 2014
Human	ALS patients	↑ Wnt3, Wnt4, Fz2, and Fz8	↑ Wnt5a ↑ Fz2	Neurons and astrocytes Neurons and astrocytes	↑ Astrocytes ↑ Astrocytes	Gonzalez-Fernandez et al., 2019

↑: Upregulation/increase; ↓: downregulation/decrease; =: no changes. ALS: Amyotrophic lateral sclerosis; aPKC: atypical protein kinase C; EOM: extraocular muscles; Fz: Frizzled; GSK-3β: glycogen synthase kinase 3β; hSOD1: human copper-zinc superoxide dismutase; iPSCs: induced pluripotent stem cells; LB: limb muscles; LRP: low-density lipid receptor-related protein; MNs: motor neurons; ND: not detailed; NE: not evaluated; Ryk: receptor-like tyrosine kinase; sFRP: secreted frizzled-related protein; Wif1: Wnt inhibitory factor 1; WT: wild-type.