Sharma N, Hewett J, Ozelius L J, Ramesh V, McLean P J, Breakefield X O, Hyman B T
Department of Neurology, Alzheimer's Disease Research Unit, and the Department of Neurology, Molecular Neurogenetics Unit, Massachusetts General Hospital East, Charlestown, Massachusetts. Albert Einstein College of Medicine, Bronx, New York.
Am J Pathol. 2001 Jul;159(1):339-44. doi: 10.1016/s0002-9440(10)61700-2.
TorsinA, a novel protein in which a mutation causes dominant, early onset torsion dystonia, may serve as a chaperone for misfolded proteins that require refolding or degradation. It has been hypothesized that misfolded alpha-synuclein, a protein in which two mutations cause autosomal dominantly inherited Parkinson's disease, serves as a nidus for the development of a Lewy body. We hypothesized that torsinA plays a role in the cellular processing of alpha-synuclein. We demonstrate that anti-torsin antibodies stain Lewy bodies and Lewy neurites in the substantia nigra and cortex. Using sensitive fluorescent resonance energy transfer (FRET) techniques, we find evidence of a close association between torsinA and alpha-synuclein in Lewy bodies.
扭转蛋白A是一种新型蛋白质，其突变会导致显性早发性扭转性肌张力障碍，它可能作为需要重新折叠或降解的错误折叠蛋白的伴侣蛋白。据推测，错误折叠的α-突触核蛋白（该蛋白的两个突变会导致常染色体显性遗传帕金森病）是路易小体形成的病灶。我们推测扭转蛋白A在α-突触核蛋白的细胞加工过程中发挥作用。我们证明抗扭转蛋白抗体可使黑质和皮质中的路易小体和路易神经突染色。使用灵敏的荧光共振能量转移（FRET）技术，我们发现路易小体中扭转蛋白A和α-突触核蛋白之间存在紧密关联的证据。
