Jensen P H, Nielsen M S, Jakes R, Dotti C G, Goedert M
Department of Medical Biochemistry, Building 170, University of Aarhus, DK-8000 Aarhus C, Denmark.
J Biol Chem. 1998 Oct 9;273(41):26292-4. doi: 10.1074/jbc.273.41.26292.
The presynaptic protein alpha-synuclein has been implicated in the pathogenesis of Parkinson's disease. First, two missense mutations A30P and A53T cause inheritable early onset Parkinson's disease in some families. Secondly, alpha-synuclein is present in Lewy bodies of affected nerve cells in the predominant sporadic type of Parkinson's disease as well as in dementia with Lewy bodies. We demonstrate in the rat optic system that a portion of alpha-synuclein is carried by the vesicle-moving fast component of axonal transport and that it binds to rat brain vesicles through its amino-terminal repeat region. We find alpha-synuclein with the A30P mutation of familial Parkinson's disease devoid of vesicle-binding activity and propose that mutant alpha-synuclein may accumulate, leading to assembly into Lewy body filaments.
突触前蛋白α-突触核蛋白与帕金森病的发病机制有关。首先，两个错义突变A30P和A53T在一些家族中导致遗传性早发性帕金森病。其次，在帕金森病主要的散发性类型以及路易体痴呆中，α-突触核蛋白存在于受影响神经细胞的路易小体中。我们在大鼠视觉系统中证明，一部分α-突触核蛋白由轴突运输的快速移动囊泡成分携带，并且它通过其氨基末端重复区域与大鼠脑囊泡结合。我们发现家族性帕金森病的A30P突变的α-突触核蛋白缺乏囊泡结合活性，并提出突变的α-突触核蛋白可能会积累，导致组装成路易小体细丝。
