Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell "suicide" enzymes are a missing link in Alzheimer’s disease

29.07.2003


Northwestern University researchers have found that caspases, a family of protein-cutting enzymes involved in programmed cell death (apoptosis), may be a missing link in the chain of molecular events leading to Alzheimer´s disease.
Alzheimer´s disease is a neurodegenerative condition affecting an estimated 4 million Americans that causes memory loss and, ultimately, dementia. Patients with this disease have abnormal deposits (plaques) of protein fragments called amyloid-beta surrounding neurons in their brain and "tangles" of a protein called tau inside brain cells.

For years, scientists have been debating which of these two events – plaques or tangles – is the primary cause of Alzheimer´s disease. Recent studies have suggested that amyloid promotes the assembly of tau into tangles, but, until now, the actual mechanism by which this occurs was poorly understood.


In an article appearing in the online version of the Proceedings of the National Academy of Sciences, co-senior authors Lester I. Binder and Vincent L. Cryns of the Feinberg School of Medicine at Northwestern University report that caspases may provide a direct link between amyloid and tangles.

Because caspases were known to be activated in dying neurons in Alzheimer´s disease and to cut (cleave) tau under some circumstances, Binder and Cryns reasoned that caspases might be responsible for cleaving tau into smaller or truncated forms that are often observed in tangles.

In a collaboration between their two labs, the scientists demonstrated that exposing neurons to amyloid-beta activates caspases, which then cleave tau at a specific site (Asp421) in the tail end of the molecule. They then showed that this truncated form of tau was much more prone to forming abnormal filaments that resemble tangles, suggesting that amyloid exposure might promote tangle formation through the action of caspases on tau.

To provide additional evidence of the relevance of their findings to Alzheimer´s disease, Binder and Cryns also created a monoclonal antibody that specifically recognizes the truncated form of tau produced by caspases. With this antibody, they demonstrated that tau is commonly cleaved at this site in the tangles in Alzheimer´s disease, indicating that caspase cleavage of tau may play a role in tangle formation in this disease.

By suggesting a new link between the two major brain abnormalities in Alzheimer´s disease, Binder and Cryns hope their work will "provide a common ground between the amyloid and tau proponents and point to the need to consider both of these interrelated pathological events in future studies and therapies."

Indeed, in ongoing studies in their laboratories, they hope to establish the timing of tau cleavage in Alzheimer´s disease brains relative to other molecular events and to determine what role, if any, caspase cleavage of tau has in neuronal cell death.

Binder is professor of cell and molecular biology and a researcher at the Cognitive Neurology and Alzheimer´s Disease Center at the Feinberg School. Cryns is assistant professor of medicine and director of the Cell Death Regulation Laboratory in the department of medicine at the Feinberg School. Their co-researchers on this study include: T. Chris Gamblin; Feng Chen; Angara Zambrano; Aida Abraha; Sarita Lagalwar; Angela L. Guillozet; Meling Lu; Yifan Fu; Francisco Garcia-Sierra; Nichole LaPointe; Richard Miller; and Robert W. Berry, professor of cell and molecular biology.

Elizabeth Crown | EurekAlert!
Further information:
http://www.nwu.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

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...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

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

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>