Hoffner Guylaine, Djian Philippe
UPR 2228-CNRS, Institut Interdisciplinaire des Sciences du Vivant des Saints-Pères, Université René-Descartes, 45, rue des Saints-Pères, 75270 cedex 6, Paris, France.
Biochimie. 2002 Apr;84(4):273-8. doi: 10.1016/s0300-9084(02)01398-6.
The presence of an expanded polyglutamine produces a toxic gain of function in huntingtin. Protein aggregation resulting from this gain of function is likely to be the cause of neuronal death. Two main mechanisms of aggregation have been proposed: hydrogen bonding by polar-zipper formation and covalent bonding by transglutaminase-catalyzed cross-linking. In cell culture models of Huntington's disease, aggregates are mostly stabilized by hydrogen bonds, but covalent bonds are also likely to occur. Nothing is known about the nature of the bonds that stabilize the aggregates in the brain of patients with Huntington's disease. It seems that the nature of the bond stabilizing the aggregates is one of the most important questions, as the answer would condition the therapeutic approach to Huntington's disease.
多聚谷氨酰胺的扩增会在亨廷顿蛋白中产生毒性功能获得。这种功能获得导致的蛋白质聚集很可能是神经元死亡的原因。已经提出了两种主要的聚集机制：通过极性拉链形成的氢键和转谷氨酰胺酶催化的交联形成的共价键。在亨廷顿病的细胞培养模型中，聚集体大多通过氢键稳定，但共价键也可能会出现。对于稳定亨廷顿病患者大脑中聚集体的化学键性质尚无了解。稳定聚集体的化学键性质似乎是最重要的问题之一，因为答案将决定亨廷顿病的治疗方法。
