A neurodegenerative disease affecting synaptic connections in Drosophila mutant for the tumor suppressor morphogen Patched.

ABSTRACT: The tumor suppressor morphogen, Patched (Ptc), has an extensive homology to the Niemann-Pick-C 1 (NPC1) protein. The NPC disease is a paediatric, progressive and fatal neurodegenerative disorder thought to be due to an abnormal accumulation of cholesterol in neurons. Here, we report that patched mutant adults develop a progressive neurodegenerative disease and their brain contains membranous and lamellar inclusions. There is also a significant reduction in the number of synaptic terminals in the brain of the mutant adults. Interestingly, feeding cholesterol to wild type flies generates inclusions in the brain, but does not cause the disease. However, feeding cholesterol to mutant flies increases synaptic connections and suppresses the disease. Our results suggest that sequestration of chol

SUBMITTER: Gazi M 

PROVIDER: S-EPMC2760493 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature