tailieunhanh - Báo cáo khoa học: PA700, the regulatory complex of the 26S proteasome, interferes with a-synuclein assembly

Parkinson’s disease is characterized by the loss of dopaminergic neurons in the nigrostriatal pathway accompanied by the presence of intracellular cytoplasmic inclusions, termed Lewy bodies. Fibrillized a-synuclein forms the major component of Lewy bodies. We reported a specific interaction between rata-synuclein and tat binding protein 1, a subunit of PA700, the regulatory complex of the 26S proteasome. | ềFEBS Journal PA700 the regulatory complex of the 26S proteasome interferes with a-synuclein assembly Medeva Ghee1 Ronald Melki2 Nadine Michot3 and Jacques Mallet1 1 Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs Centre Nationalde la Recherche Scientifique Hopital de la Pitie Salpetriere Paris France 2 Laboratoire d Enzymologie et Biochimie Structurales Centre Nationalde la Recherche Scientifique France 3 Protein Production Aventis Pharma Vitry France Keywords a-synuclein aggregation PA700 proteasome tat binding protein Correspondence M. Ghee Laboratoire de Genetique Moleculaire de la Neurotransmission et des Processus Neurodegeneratifs Centre Nationalde la Recherche Scientifique UMR7091 Batiment CERVI Hopitalde la Pitie Salpetriere 83 boulevard de l Hopital 75013 Paris France Fax 33 1 42 17 75 33 Tel 33 1 42 17 75 42 Email mghee@ R. Melki Laboratoire d Enzymologie et Biochimie Structurales Centre National de la Recherche Scientifique 91198 Gif-sur-Yvette Cedex France Fax 33 1 69 82 35 04 Tel 33 1 69 82 35 03 E-mail melki@ Received 28 February 2005 revised 20 April2005 accepted 16 May 2005 Parkinson s disease is characterized by the loss of dopaminergic neurons in the nigrostriatal pathway accompanied by the presence of intracellular cytoplasmic inclusions termed Lewy bodies. Fibrillized a-synuclein forms the major component of Lewy bodies. We reported a specific interaction between rat a-synuclein and tat binding protein 1 a subunit of PA700 the regulatory complex of the 26S proteasome. It has been demonstrated that PA700 prevents the aggregation of misfolded nonubiquinated substrates. In this study we examine the effect of PA700 on the aggregation of wildtype and A53T mutant a-synuclein. PA700 inhibits both wild-type and A53T a-synuclein fibril formation as measured by Thioflavin T fluorescence. Using size exclusion chromatography we present evidence for a stable PA700-a-synuclein .

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