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
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy