title: Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease.
abstract: Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis.
authors.affiliation: Molecular Genetics Unit, National Institutes on Aging, Bethesda, MD, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Bras
authors.forename: Andrew
authors.initials: A
authors.lastname: Singleton
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
authors.forename: John
authors.initials: J
authors.lastname: Hardy
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002518:Ceramides / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016631:Lewy Bodies / Q000378:metabolism; D020961:Lewy Body Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D000077296:Niemann-Pick C1 Protein; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D051102:Serine C-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D051844:alpha-Synuclein / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D002518:Ceramides; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; C497604:SNCA protein, human; D051844:alpha-Synuclein; C487784:SPTLC1 protein, human; D051102:Serine C-Palmitoyltransferase; D010770:Phosphotransferases