Frontotemporal dementia is characterized by the progressive degeneration of the frontal and temporal lobes in the brain. This disease is caused, among other potential and known mutations, by the haploinsufficiency of the GRN gene, which is responsible for making progranulin. Progranulin is cleaved into lysosomal granulin polypeptides.
It is not clear why the absence of properly functioning lysosomal granulins causes neurodegeneration.
A recent paper studied progranulin-deficient human cells and murine brains, and human frontal lobes from GRN-mutation FTD patients. The authors discovered increased levels of gangliosides, glycosphingolipids that contain sialic acid in the samples.
Turns out, granulins are required to maintain bis(monoacylglycero)phosphates levels to support ganglioside catabolism, and that progranulin deficiency in lysosomes leads to gangliosidosis.
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#gangliosidosis #MassSpec #lipid #lipidomics
