Abnormal lipid degradation in lysosomes of Alzheimer’s brain
Bis(monoacylglycero)phosphate (BMP) is an unusual phospholipid of lysosomes that is required for degradation of numerous lipids including gangliosides. Two chiral glycerol carbons in the S (rather than the R) stereo-conformation, protects BMP from lysosomal degradation. Alterations in BMP levels are associated with neurodegenerative diseases.
The researchers discover that lysosomal S,S-BMP is synthesized by phospholipases D3 and D4 and that these enzymes linked to neurodegeneration are required for degradation of ganglioside lipids.
PLD3 mutants associated with neurodegenerative diseases, including risk of Alzheimer’s disease, diminished PLD3 catalytic activity.
