Photo credit: Cristian Newman/Unsplash.com
Date: 17 July 2020
Institution: University of Göttingen
Study published in: Biochemistry
Digest: Research develops new inhibitors for enzymes that is part of the human brain’s hormone metabolism plays a critical pathophysiological role in the development of Alzheimer’s disease.
Due to pathological changes in the brain, patients with Alzheimer’s disease become increasingly forgetful and disoriented as the disease progresses. In the worst cases, even close relatives are no longer recognized and simple household tasks can no longer be carried out independently. This means care is needed for those affected. Despite intensive research, Alzheimer’s disease is still considered incurable today. Researchers at the University of Göttingen and the Fraunhofer Institute for Cell Therapy and Immunology Leipzig-Halle have described a promising approach to treating Alzheimer’s disease.
For the study, Professor Kai Tittmann from the Göttingen Centre for Molecular Biosciences worked together with researchers from the Faculty of Chemistry at the University of Göttingen and the team led by Professor Hans-Ulrich Demuth from Fraunhofer IZI in Halle. Several years ago, the team from Halle discovered that a specific enzyme that is part of the human brain’s hormone metabolism plays a critical pathophysiological role in the development of Alzheimer’s disease, in addition to its actual biological function of hormone maturation. The first inhibitors of this enzyme, which inhibit specific pathological processes, have already produced promising results.
In order to give these active ingredients a chemical “tailor-made suit”, the research team investigated the enzyme’s reaction mechanism using protein crystallography. “This enabled us to obtain ‘snapshots’ of the working enzyme for the first time,” says senior author Tittmann. This made it possible to build novel inhibitors where the principle of the design is based on the natural reaction. These inhibitors therefore lead to highly selective binding without the risk of dangerous side effects. The scientists also succeeded in determining an atomic structure of the human enzyme with the new substance. This forms an important basis for further development of the inhibitors. “We are confident that our results will lead to the development of a new, highly selective generation of Alzheimer’s drugs,” explained Demuth.
The research project was funded by the German Research Foundation (DFG), the Federal Ministry of Economic Affairs and Energy and the Alzheimer Forschung Initiative e.V.
Source: University of Göttingen
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