Gangliosides as Therapeutic Targets for Neurodegenerative Diseases

Table 1

Alteration of the ganglioside levels which affect the neuropathology of the neurodegenerative disorders.

Disorder	Species	Model	Ganglioside alterations	Clinical signs	References
AD	Human	Early-onset AD	Total ganglioside	Lower ganglioside level in frontal white and gray matter.	[14]
AD	Human	Late-onset AD	Total ganglioside	Lower ganglioside level in temporal cortex, hippocampus, and frontal white matter of patients.	[14]
AD	Human	AD	GD1b, GT1b	Reduction ganglioside in hippocampal gray matter.	[15]
AD	Mouse	1XFAD/GM2S^-/-	GM3, GD3	Exacerbation of Alzheimer’s pathology	[9]
AD	Mouse	2XFAD/GD3S^-/-	GM1, GD1a, GM3	Amelioration of disease pathology	[16]
AD	Mouse	5XFAD/GM3S^-/-	Lack of major gangliosides	Lower Aβ deposition and neuroinflammation	[17]
AD	Mouse	5xFAD//Ugcgf/f//Thy1-CreERT2//EYFP	GM3, GM2, GT1b	Improve memory and loss of dendritic spines	[18]
PD	Human	PD	GM1	Reduction of GM1 in occipital cortex	[19]
PD	Human	PD	GM1, GD1a	Reduction of gangliosides in heart, colon, and skin tissues.	[20]
PD	Mouse	B4GALNT1^-/-	GM3, GD3	Accumulation of αSyn deposition in SN.	[21]
PD	Mouse	B4GALNT1^+/-	GM1, GD1a, GD1b	PD-like motor functions and αSyn accumulation	[11]
HD	Human	HD	GM1	Reduction of GM1 in fibroblast.	[10]
HD	Human	HD	GM1	Increased GM1 in the cerebellum.	[22]
HD	Human	HD	ST8Sia3 and B4Galnt1	Decreased expression of ganglioside synthesis enzymes in the brain.	[23]
HD	Mouse	R6/1	GM1	Molecular, behavioral, and motor disturbances	[22]
HD	Mouse	YAC128	GM1, GD1a, GT1b	Neurodegeneration and motor function abnormalities	[10]
ALS	Human	ALS	GM2	Increased GM2 in the motor cortex	[24]
ALS	Human	ALS	GM3 and GM1	Increased GM3 and GM1 in spinal cord.	[13]
ALS	Mouse	SOD1^G93A	GM3	Gait impairment and reduced motor function	[13]
ALS	Mouse	SOD1^G86R	GM1a, GM2, GM3	Spinal motor neuron degeneration, progressive skeletal muscle weakness	[25]
HSP	Mouse	B4GALNT1^-/-	GM3, GD3	Deficiency of hippocampal plasticity, axonal degeneration	[26, 27]