Normal dopaminergic nigrostriatal innervation in SPG3A hereditary spastic paraplegia.
SPG3A/atlastin-1 gene mutations cause an autosomal dominant form of hereditary spastic paraplegia (SPG3A-HSP). We used positron emission tomography with [(11)C]DTBZ to assess nigrostriatal dopaminergic integrity in two unrelated adults with SPG3A-HSP due to the common SPG3A/atlastin-1 mutation, R239C. Nigrostriatal dopaminergic terminal density was normal. A difference from the human pattern of neurodegeneration is a critical limitation of this Drosophila model of SPG3A-HSP. This major difference between human SPG3A/atlastin-1 mutations and the Drosophila atl(l) phenotype has several possible explanations.
Albin
Roger L
RL
Geriatrics Research, Education, and Clinical Center, Ann Arbor VAHS, Ann Arbor, Michigan 48109-2200, USA. ralbin@umich.edu
Koeppe
Robert A
RA
Rainier
Shirley
S
Fink
John K
JK
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins; D006801:Humans; D008565:Membrane Proteins; D009154:Mutation; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics* / Q000378:metabolism*; D013378:Substantia Nigra / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000378:metabolism
D015415:Biomarkers; D002250:Carbon Radioisotopes; D008565:Membrane Proteins; D019275:Radiopharmaceuticals; C032811:dihydrotetrabenazine; C440006:ATL1 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D004298:Dopamine; D013747:Tetrabenazine