Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Protein Repairs Nerve Cell Damage


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.

Source: S. Weyer, IPMB

Production of APPsα in the brain: The nerve cells that encounter viral gene shuttles produce the therapeutic APPsα protein (orange) along with a green fluorescent protein. Brain region: hippocampus, important for learning and memory.

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).

Original publication:
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
Press Office
Phone +49 6221 54-2311

Weitere Informationen:

Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>