Leźnicki Paweł
Department of Molecular and Cellular Biology, Intercollegiate Faculty of Biotechnology, University of Gdańsk, Gdańsk, Poland.
Postepy Biochem. 2005;51(2):215-22.
Expansion of CAG triplet repeats is a cause of at least nine late-onset neurodegenerative disorders. The mutation manifests itself as a long stretch of glutamine repeats. The number of approximately 38 repeats is usually a threshold at which the disease develops and the longer the polyglutamine tract, the earlier the onset of disease. A common feature of these disorders is the presence of protein aggregates which are believed to be formed either by the formation of hydrogen bonds between amide residues or through the action of the enzyme transglutaminase. Mutated proteins may cause neurodegeneration by sequestering vital cellular proteins, inhibiting proteasomal system or by inducing apoptosis. It has been proved that molecular chaperones may block the negative effects of expression of mutated genes and for this reason they are a promising object for various therapeutic research.
CAG三联体重复序列的扩增是至少九种迟发性神经退行性疾病的病因。该突变表现为一段长的谷氨酰胺重复序列。大约38次重复通常是疾病发生的阈值，聚谷氨酰胺序列越长，疾病发作越早。这些疾病的一个共同特征是存在蛋白质聚集体，据信这些聚集体是由酰胺残基之间形成氢键或通过转谷氨酰胺酶的作用形成的。突变蛋白可能通过隔离重要的细胞蛋白、抑制蛋白酶体系统或诱导细胞凋亡来导致神经退行性变。已经证明分子伴侣可能会阻断突变基因表达的负面影响，因此它们是各种治疗研究的一个有前景的对象。
