Glucocerebrosidase

2022-07-06: reference:

Glucocerebrosidase #

• Lysosomal β-Glucocerebrosidase hydrolyzes the β-glycosidic linkage of Glucocerebroside.

• Insulin Resistance leads to deficits in glucocerebrosidase, causing defects in glycogen processing. The dysfunction of glucocerebrosidase leads to accumulation of ceramides/gangliosides. This leads to astrocytic swelling.

• Glucocerebrosidase supports the formation of the autophagesome and autophagesome formation is supported by Mtorc2 which requires insulin signalling to promote protein synthesis. its this failure of glucocerebrosidase which promotes the accumulation of ceramides and gangliosides within the brain and dysfunction of lysosomal quality

  • The Cross-Talk Between Sphingolipids and Insulin-Like Growth Factor Signaling: Significance for Aging and Neurodegeneration
    • (C1P = ceramide-phosphatel CerK=Ceramide kinase; CerS = Synthase)
    • Sphingosine/ceramide-1-phosphate are the bioactive mediators; I believe they act only as signals and don’t constitute the membrane. It binds to the GPCR S1PR1, other transmembreane domains, including those within the lipid bilayer.