Channel problems in Niemann-Pick disease

The inhibition of cellular calcium channel activity by lipids that accumulate in cells of patients with Niemann-Pick disease could underlie the disease, reports a paper published in Nature Communications this week. The study, which provides a molecular link between lipid accumulation and abnormal function of cells, could assist in the development of new approaches to the treatment Niemann-Pick and related diseases known as lysosomal storage diseases. The lysosome serves as the cell’s recycling centre as it degrades a variety of molecules. Niemann-Pick disease and over 50 similar genetic diseases result in the accumulation of molecules, such as sphingomyelin, in cellular lysosomes. One consequence of this accumulation is problems with the handing of calcium ions within cells. Haoxing Xu and his colleagues found that the activity of the lysosomal calcium channel TRPML1 was reduced in skin cells of patients with Niemann-Pick disease. The inhibition was caused by sphingomyelins that had accumulated in lysosomes. The team discovered that reactivating the enzyme that was lost as a result of the genetic defect in these patients, increased the activity of TRPML1 in cultured cells. The work suggests that activation of TRPML1 may provide a novel therapeutic approach for Niemann-Pick disease and related lysosomal storage diseases.