Cultured hippocampal neurons that have accumulated GlcCer (right), using a chemical inhibitor of glucocerebrosidase, release more
calcium from internal stores than their control counterparts (left).
|
We are attempting to delineate the molecular mechanisms by which sphingolipid accumulation in lysosomal storage diseases causes cell dysfunction, specifically in neuronal cells. We have shown that neuronal Ca2+-homeostasis is altered in models of Gaucher, Tay-Sachs (Sandhoff) and Niemann-Pick diseases, and we are currently attempting to determine the precise biochemical mechanisms by which sphingolipids alter
Ca2+-homeostasis.
|