Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Tiny but toxic: MBL researchers discover a mechanism of neurodegeneration in Alzheimer's disease

31.03.2009
Tiny, toxic protein particles severely disrupt neurotransmission and inhibit delivery of key proteins in Alzheimer's disease, two separate studies by Marine Biological Laboratory (MBL) researchers have found.

The particles are minute clumps of amyloid beta, which has long been known to accumulate and form plaques in the brain of Alzheimer's patients.

"These small particles that haven't aggregated into plaques—these are increasingly being seen as the really toxic species of amyloid beta," says Scott Brady of University of Illinois College of Medicine, who has been an MBL investigator since 1982.

Brady and his colleagues found that these particles inhibit neurons from communicating with each other and with other target cells in the body.

"The disease symptoms for Alzheimer's are associated not with the death of the neurons – that is a very late event – but with the loss of functional connections. It's when the neuron is no longer talking to its targets that you start to get the memory deficits and dementia associated with the disease," Brady says.

The amyloid beta particles activate an enzyme, CK2, which in turn disrupts the "fast axonal transport" system inside the neuron, Brady found. This transport system has motor proteins that move various kinds of cargo (including neurotransmitters and the associated protein machinery for their release) from place to place in the neuron on microtubule tracks.

Brady's findings are complemented by a new study by Rudolfo Llinás of New York University School of Medicine. Brady and Llinás both conduct neuroscience research at the MBL using the giant nerve cell of the Woods Hole squid, Loligo paeleii, as a model system.

Llinás found that activation of CK2 blocks neurotransmission at the synapse – the point where the neuron connects to its target.

"Disruptions in the fast axonal transport system are probably key elements in the pathogenesis of Alzheimer's and other adult-onset neurodegenerative diseases, such as Parkinson's and ALS," says Brady. "It doesn't mean that is the only thing going on, or that it is the triggering feature of the disease. But we do know that changes in the fast axonal transport system are sufficient to cause the 'dying back' of neurons that is characteristic of these diseases."

The new findings suggest the possibility of designing a drug to inhibit CK2 activation in Alzheimer's patients. However, a prior study by Brady found that activation of another enzyme, GSK3, in Alzheimer's also disrupts the fast axonal transport system. It may therefore be necessary to inhibit both enzymes.

"There haven't yet been any therapies designed for Alzheimer's with the idea of protecting the fast axonal transport system," says Brady. "But if there were, they would have to inhibit the activation of both CK2 and GSK3. We can't think of it as a single thing going wrong. There are several things going wrong."

Citations:

Pigino, G., et al. (2009) Disruption of fast axonal transport is a pathogenic mechanism for intraneuronal amyloid beta. PNAS: doi 10.1073/pnas0901229106.

Moreno, H. et al. (2009) Synaptic transmission block by presynaptic injection of oligomeric amyloid beta. PNAS: doi 10.1073/pnas09000944106.

Background information:

Lapointe, N.E., et al. (2009) The amino terminus of tau inhibits kinesin-dependent axonal transport: Implications for filament toxicity. J. Neurosci. Res. 87(2): 440-451.

The MBL is a leading international, independent, nonprofit institution dedicated to discovery and to improving the human condition through creative research and education in the biological, biomedical and environmental sciences. Founded in 1888 as the Marine Biological Laboratory, the MBL is the oldest private marine laboratory in the Western Hemisphere.

Diana Kenney | EurekAlert!
Further information:
http://www.mbl.edu

More articles from Life Sciences:

nachricht Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Safe glide at total engine failure with ELA-inside

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.

On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

New pop-up strategy inspired by cuts, not folds

27.02.2017 | Materials Sciences

Sandia uses confined nanoparticles to improve hydrogen storage materials performance

27.02.2017 | Interdisciplinary Research

Decoding the genome's cryptic language

27.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>