Sacsin, a multidomain molecular chaperone involved in neurodegenerative disease

蛋白质是构成机体功能的基本生物分子。蛋白质必须折叠成复杂的三维形状才能正常工作。不能正确折叠的蛋白质被“质量控制”系统检测到，然后通过降解处理掉。这种蛋白质的折叠和受控破坏涉及一组特殊的蛋白质，称为分子伴侣。这项工作的重点是sacsin，一种新的蛋白质，这是能够调节分子伴侣机器。Sacsin在大脑中具有重要作用，因为其基因突变会导致遗传性神经元疾病。为了了解更多关于分子伴侣的生物学知识，并理解为什么sacsin突变会导致疾病，我们正在研究它在细胞中的确切功能。Sacsin的功能正在通过一系列全面的实验来研究。我们正在寻找它的位置，它与哪些其他蛋白质相互作用，以及当它缺失时会发生什么。研究sacsin很重要，因为蛋白质折叠的问题会导致折叠不良的蛋白质积累的疾病，包括阿尔茨海默病和帕金森病。更重要的是，分子伴侣与这些疾病有关，在实验模型中可以减缓疾病进展。

Proteins are the essential biological molecules that build the machines which make the body function. Proteins must be folded into complex three dimensional shapes to work properly. Proteins that do not fold correctly are detected by ‘quality-control’ systems and are then disposed of by being degraded. This folding and controlled destruction of proteins involves a special group of proteins known as molecular chaperones. This work is focused on sacsin, a novel protein, which is able to regulate a molecular chaperone machine. Sacsin has an important role in the brain as mutations in its gene cause an inherited neuronal disease. To find out more about the biology of molecular chaperones and understand why mutations in sacsin cause disease we are investigating its precise function in cells. Sacsin’s function is being looked at through a comprehensive series of experiments. We are finding out where it’s located, what other proteins it interacts with and what happens when it’s absent. Studying sacsin is important because problems with protein folding lead to diseases where badly folded proteins accumulate; these include Alzheimer’s and Parkinson’s disease. What’s more molecular chaperones are associated with these conditions and in experimental models can slow disease progression.