Gangliosides as Therapeutic Targets for Neurodegenerative Diseases.

Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP).

Lithium treatment rescues dysfunctional autophagy in the cell models of Tay-Sachs disease.

Tay-Sachs disease is a rare lysosomal storage disorder (LSD) caused by a mutation in the HexA gene coding β-hexosaminidase A enzyme. The disruption of the HexA gene causes the accumulation of GM2 ganglioside resulting in progressive neurodegeneration in humans. Surprisingly, Hexa-/- mice did not show neurological phenotypes.

Analysis of Brain Lipids in the Early-Onset Tay-Sachs Disease Mouse Model With the Combined Deficiency of β-Hexosaminidase A and Neuraminidase 3.

Tay-Sachs disease is an autosomal recessively inherited lysosomal storage disease that results from loss-of-function mutations in the gene coding β-hexosaminidase A. gene deficiency affects the central nervous system owing to GM2 ganglioside accumulation in lysosomes resulting in progressive neurodegeneration in patients. We recently generated a novel mice model with a combined deficiency of β-hexosaminidase A and neuraminidase 3 () that mimics both the neuropathological and clinical abnormalities of early-onset Tay-Sachs disease.