Table 1.

Role of lithium and Wnt signaling in neurodegenerative and demyelinating diseases as well as CNS injuries

CNS disease	Studied molecule	Molecular function	Effects in the nervous sytem	References
Mood disorder	GSK3β gene variant or copy number	Inhibition of β catenin	Increases the risk of bipolar disorder	[148, 149]
	GSK3β activation	Inhibition of β catenin	Mania	[155, 156]
	GSK3β inhibition	Activation of β catenin	Antidepressant. anti-maniac	[124, 152, 153]
	Lithtum	Dissociates the interaction of βamecstin2 and PP2A	Inhibits the behavioral action of dopamine	[124]
	FZD3, GSK-3IV and DKK4	Involved m Wnt pathway	Correlated with risk of schizophrenia	[163–165]
	APC	Negative regulator of Wnt signaling	Associated with schizophrenia	[106–168]
	Lithium	Inhibition of GSK36	Clinical effect in patients	[169]
	DJSC1 and Dixdc1	Involved neuronal progenitor proliferation and regulate Wnt pathway	Associated with schizophrenia and bipolar disorder symptoms	[172, 176–179]
	Wn12	Involved miR16 expression	Anti-apoptotic	[181, 182]
Alzheimer’s	GSK3β activity	Reduces βcatenin level	Increased in AD patients	[183, 184]
Disease	Wni3A and Lithium	Inhibition of GSK3β	Decreases Aβ production and in vitro toxicity	[185–189]
	Lithium	Inhibition of GSK3β	Regulates tau degradation	[190–195, 198–200]
	Lithium	Inhibition of GSK3β	Improves behavioral deficit in mouse model for AD	[186, 196, 197]
	FZD1	Receptor for Wnt	Binds t0 Aβ; reduces Aβ neurotoxicity	[202, 203]
	Dkk1	Wnt antagonist	Participates in Aβ toxicity. increased in AD patients	[204–206]
	M1 mAChR	Muscarinic receptor able to inhibits GSK3β	Activates Wnt pathway. and reverses Aβ toxixity	[209]
	IBU-PO, IL1β blocking	Inhibit inflammatory effects of GSK3 < i	Protects against Aβ in vitro and ameliorates AD mouse symptoms	[211, 212]
	Lithium	Inhibition of GSK3β	Clinical use in AD	[214–219]
Huntington disease	Lithium	Inhibition of GSK3β	Reduces apoptosis and huntingtin degradationcaipain inhibitioninduction of autophagy	[222–225][226][227]
	βcatenin	Transducer of the Wnt pathway	Stabilized by huntingtinimproves motor and behavioral performance and exerts neuroprotective effects in animal models of HO	[228][229–233]
Parkinson’s disease	Lithium	Inhibition of GSK3β	Neuroprotective effects in vitroneuroprotective effects in animal model of PDprotection against oxidative stress activates autophagic pathway	[235–237][238–241][242, 243][244, 245]
	Dkk 1	Wnt antagonist	Induces neurotoxicity	[247]
Traumatic brain injury	Lithium	Inhibition of GSK3β	Prevent depression behavioranti-inflammatory. anti-edematous effects, memory improvementneuroprotection, anti-inflammatory motor recuperation, reduced anxiety	[256][257][258–261]
Demyelinating diseases	Lithium	Inhibition of GSK3D	Reduces demyeimation inflammation and progression of the disease in models of multipte sclerosis	[263, 264]
	Axin2	Negative regulator ol Wnt signaling	Associated with multiple sclerosis lesions, promotes remyelination	[265]
	ARA-014418. lithium indirubin, and 1803-mt	GSK3β inhibitors	Stimulate oligodendrocyte regeneration and promote remyelination	[266]
	GSK3β variant	Inhibition of GSK3β	Associates with multiple sclerosis	[267]
	Lithium	Inhibition of GSK3β	Stimulates peripheral myelin gene expression and promotes nerve remyelination	[14]
	Lithium chloride and citrate	Decrease N-acetyl aspartate	Counteracts neurodegeneration and dysmyelination in Canavan disease	[269–272]