Experiments by Heidelberg researchers provide insight into novel gene therapy approach to treat Alzheimer’s
In laboratory experiments on the basic mechanisms that cause Alzheimer’s dementia, an international research team led by Heidelberg neurobiologist Prof. Dr. Ulrike Müller and a team of French scientists have succeeded in largely “repairing” the nerve cell damage typical in this disease.
The researchers took a closer look at a key protein in Alzheimer’s pathogenisis, APP, and one of its cleavage products APPsα. Prof. Müller of Heidelberg University’s Institute of Pharmacy and Molecular Biotechnology explains that viral gene shuttles were used to drive the delivery of APPsα into the brains of Alzheimer´s mouse models.
The protein APPsα in turn elicited repair effects and clearly improved memory. The researchers hope to use these findings to explore new approaches in the development of gene therapy for Alzheimer’s. Their results were published in the journal “Acta Neuropathologica”.
Alzheimer’s is the most frequent cause of dementia in the elderly. It particularly affects regions of the brain that are fundamental for memory and learning. The junctions through which the nerve cells communicate, the synapses, disappear long before the nerve cells die, damage that impairs both learning and memory. “While dead nerve cells are irretrievably lost, damaged synapses can be regenerated in the elderly,” Prof. Müller emphasises.
The brains of Alzheimer’s patients show plaque deposits, she explains. The deposits thwart the communication between the nerve cells and cause them to eventually die. The main component of the plaque is a short protein fragment known as the beta amyloid peptide. It is generated when the considerably larger amyloid precursor protein, or APP, is cleaved.
“Until now, scientists believed that the overproduction of beta amyloid peptides was the main cause of Alzheimer’s. More recent investigations, however, have demonstrated that another APP cleavage product, the APPsα protein, also diminishes over the course of the disease,” Ulrike Müller continues. The protein cleaving enzymes, called secretases, play a key role in this process.
The scissor-like secretases cut the APP cell surface protein at various positions. “These cleaving processes produce beta amyloid peptides that are toxic to the nerve cells, but also produce the protective APPsα cleavage product, which counteracts the toxic peptide,” says Prof. Müller. “Research over the last few years indicates that a misregulation of the secretase cleavage in Alzheimer’s results in inadequate production of protective APPsα.”
Earlier studies by Müller’s research group had already shown that APPsα has an essential function in the nervous system, particularly because it regulates the formation and function of synaptic junctions and spatial memory. These findings were used to investigate a new approach for a possible gene therapy for Alzheimer’s. The international research team used viral gene shuttles to introduce APPsα into the brains of mouse models with plaque deposits like those in Alzheimer’s.
“After introducing the APPsα, we saw that the nerve cell damage could be repaired. The number of synaptic junctions increased, and spatial memory began to function again,” reports Ulrike Müller. “Our research results show the therapeutic effectiveness of APPsα in the animal model and open up new perspectives for the treatment of Alzheimer’s.”
The research was conducted by the international ERA-NET NEURON Consortium, which is funded by the European Union. Other participants in the project include the research teams of Prof. Dr. Nathalie Cartier (University of Paris), Prof. Dr. Martin Korte (Braunschweig Technical University) and Prof. Dr. Christian Buchholz (Paul Ehrlich Institute, Langen).
R. Fol, J. Braudeau, S. Ludewig, T. Abel, S.W. Weyer, J.P. Roederer, F. Brod, M. Audrain, A.P. Bemelmans, C.J. Buchholz, M. Korte, A. Cartier, U.C. Müller: Viral gene transfer of APPsα rescues synaptic failure in an Alzheimer’s disease mouse model. Acta neuropathologica (published online on 4 November 2015), doi: 10.1007/s00401-015-1498-9
Prof. Dr. Ulrike Müller
Institute for Pharmacy and Molecular Biotechnology IPMB
Phone +49 6221 54-6717
Communications and Marketing
Phone +49 6221 54-2311
Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction