A proposed model for the pathogenesis of Niemann-Pick disease type B.

Defective ASMase and lysosomal storage could lead to a reduced ability of lysosomes to fuse with autophagosomes. This in turn could result in a partial block of autophagy maturation and defective degradation, accompanied by accumulation of autophagic vacuoles, peroxidized lipid droplets and aberrant mitochondria (autophagic stress). Additional evidence and hypotheses are more fully explained in the text. Dotted lines: proposed mechanism; solid lines: proven mechanism.