Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cleavage Product of Alzheimer's Key Protein APP Stimulates Nerve Cell

17.04.2018

Researchers discover receptor for the protein fragment APPsα mediating its physiological function

A cleavage product of the Alzheimer's APP protein stimulates nerve cell communication and memory. The protein fragment, known as APPsα, has neuroprotective properties and acts as a signal molecule on other nerve cells. But how does it influence brain functions?


Neuroprotective role of APPsα: A histological section through the hippocampus is depicted in the background. The red staining shows APPsα in neuronal cell bodies. The green staining shows the dendritic processes of nerve cells. Synaptic contacts between neurons are depicted as filled circles along the dendrites.

Source: Max Richter, Müller research group

An international research team led by Prof. Dr Ulrike Müller of Heidelberg University has gained new insights into the molecular mechanism underlying its physiological functions. The researchers discovered a receptor for APPsα, which paves the way for new treatment approaches for Alzheimer's.

Alzheimer's disease (AD) is triggered by insoluble protein aggregates that are found as extracellular deposits in the brain of patients suffering from AD. The main component is the β-amyloid peptide (Aβ), which damages and eventually kills the nerve cells. This small peptide is a cleavage product of a substantially larger precursor protein, the amyloid precursor protein (APP).

Alzheimer's was long assumed to be caused mainly by the overproduction of the β-amyloid peptide. "New studies show, however, that APPsα levels drop over the course of the disease. APPsα functions as an antagonist to the damaging Aβ," explains Prof. Müller. "In Alzheimer's, there is a misregulation in APP cleavage whereby too little APPsα is produced."

To find out how the neuroprotective APPsα affects brain functions, the soluble protein fragment APPsα was introduced via viral "vectors" into the hippocampus of genetically modified mice. The hippocampus is a brain region that is considered as crucial for memory formation.

The researchers were able to demonstrate that APPsα increases the number of synaptic contacts between nerve cells. "This was associated with more efficient nerve cell communication and improved memory in learning tests," states Ulrike Müller, professor of functional genomics at the Institute for Pharmacy and Molecular Biotechnology of Heidelberg University.

Further electrophysiological experiments revealed that APPsα acts as a signaling molecule on the synaptic contacts of certain nerve cells. These synaptic contacts use the neurotransmitter acetylcholine, which is one of the most important messenger molecules for transmitting signals between nerve cells.

The protein fragment APPsα enhances signal transmission by acetylcholine receptors and increases their natural receptivity. This is the first time that researchers have identified a receptor for APPsα in an animal model. "This paves the way for new options in Alzheimer's research, such as increasing the amount of APPsα in the brain," states Prof. Müller.

Caption:
Neuroprotective role of APPsα: A histological section through the hippocampus is depicted in the background. The red staining shows APPsα in neuronal cell bodies. The green staining shows the dendritic processes of nerve cells. Synaptic contacts between neurons are depicted as filled circles along the dendrites.
Source: Max Richter, Müller research group

Original publication:
M.C. Richter, S. Ludewig, A. Winschel, T. Abel, C. Bold, L.R. Salzburger, S. Klein, K. Han, S. Weyer, A.K. Fritz, B. Laube, D.P. Wolfer, C.J. Buchholz, M. Korte and U.C. Müller: Distinct in vivo role of secreted APP ectodomain variants APPsα and APPsβ in regulation of spine density, synaptic plasticity, and cognition. EMBO Journal e98335 (16 April 2018), doi: 10.15252/embj.201798335

Contact:
Prof. Dr Ulrike Müller
Institute for Pharmacy and Molecular Biotechnology
Phone +49 06221 54-6717
u.mueller@urz.uni-hd.de

Communications and Marketing
Press Office, phone +49 6221 54-2311
presse@rektorat.uni-heidelberg.de

Weitere Informationen:

http://www.ipmb.uni-heidelberg.de/bioinfo-fkt_gen/mueller

Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>