TAILIEUCHUNG - Báo cáo khoa học: a-Synuclein–synaptosomal membrane interactions Implications for fibrillogenesis

a-Synuclein exists in two different compartments in vivo – correspondingly existing as two different forms: a mem-brane-bound form that is predominantlya-helical and a cytosolic form that is randomly structured. It has been sug-gested that these environmental and structural differences may play a role in aggregation propensity and development of pathological lesions observed inParkinson’s disease (PD). Such effects may be accentuated by mutations observed in familial PD kindreds. | Eur. J. Biochem. 271 3180-3189 2004 FEBS 2004 doi a-Synuclein-synaptosomal membrane interactions Implications for fibrillogenesis Euijung Jo1 Audrey A. Darabie1 Kyung Han1 Anurag Tandon1 3 Paul E. Fraser1 2 and JoAnne McLaurin1 4 1 Centre for Research in Neurodegenerative Diseases Departments of 2Medical Biophysics 3Medicine and 4 Laboratory Medicine and Pathobiology University of Toronto Ontario Canada a-Synuclein exists in two different compartments in vivo -correspondingly existing as two different forms a membrane-bound form that is predominantly a-helical and a cytosolic form that is randomly structured. It has been suggested that these environmental and structural differences may play a role in aggregation propensity and development of pathological lesions observed in Parkinson s disease PD . Such effects may be accentuated by mutations observed in familial PD kindreds. In order to test this hypothesis wildtype and A53T mutant a-synuclein interactions with rat brain synaptosomal membranes were examined. Previous data has demonstrated that the A30P mutant has defective lipid binding and therefore was not examined in this study. Electron microscopy demonstrated that wild-type a-synuclein fibrillogenesis is accelerated in the presence of synaptosomal membranes whereas the A53T a-synuclein fibrillogenesis is inhibited under the same conditions. These results suggested that subtle sequence changes in a-synuc-lein could significantly alter interaction with membrane bilayers. Fluorescence and absorption spectroscopy using environment sensitive probes demonstrated variations in the inherent lipid properties in the presence and absence of a-synuclein. Addition of wild-type a-synuclein to synapto-somes did not significantly alter the membrane fluidity at either the fatty acyl chains or headgroup space suggesting that synaptosomes have a high capacity for a-synuclein binding. In contrast synaptosomal membrane fluidity was decreased by .

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