thermozymocidin and Motor-Neuron-Disease

Numerous mutations that impair retrograde membrane trafficking between endosomes and the Golgi apparatus lead to neurodegenerative diseases. For example, mutations in the endosomal retromer complex are implicated in Alzheimer's and Parkinson's diseases, and mutations of the Golgi-associated retrograde protein (GARP) complex cause progressive cerebello-cerebral atrophy type 2 (PCCA2). However, how these mutations cause neurodegeneration is unknown. GARP mutations in yeast, including one causing PCCA2, result in sphingolipid abnormalities and impaired cell growth that are corrected by treatment with myriocin, a sphingolipid synthesis inhibitor, suggesting that alterations in sphingolipid metabolism contribute to cell dysfunction and death. Here we tested this hypothesis in

Topics: Animals; Disease Models, Animal; Endosomes; Fatty Acids, Monounsaturated; Female; Fibroblasts; Golgi Apparatus; Male; Membrane Proteins; Mice; Mice, Neurologic Mutants; Motor Neuron Disease; Motor Neurons; Mouse Embryonic Stem Cells; Mutation; Nervous System Malformations; Neurodegenerative Diseases; Protein Transport; Proteomics; Sphingolipids; Vesicular Transport Proteins