Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery could lead to new types of Alzheimer’s drugs

12.07.2005


A ground-breaking new research approach to understanding the cellular processes of Alzheimer’s and other degenerative diseases has revealed a promising pathway to the development of new types of drugs for these diseases.



The discovery, made in the laboratory of Ratnesh Lal, research scientist in the Neuroscience Research Institute (NRI) at the University of California, Santa Barbara, is published in this week’s online issue of the Proceedings of the National Academy of Sciences (PNAS).

The research describes a new way of understanding the degeneration of brain cells in patients with Alzheimer’s, Huntington’s, and Parkinson’s diseases, as well as other degenerative diseases. Misfolded proteins in the cell membrane, and subsequent changes in the electrical properties of cells, provide the explanation for the cell degeneration. Specific three-dimensional structures of misfolded proteins are embedded in the cell membrane.


"It has long been thought that amyloid plaque, which has been studied for 30 years, was the cause of Alzheimer’s disease," said Lal. "Plaque isn’t the cause." He explained that the fibers of plaque are too large to directly affect small cells.

The answers may come from small globs of misshapen, misfolded proteins that make well-defined holes in cell membranes and disrupt their electrical activity, according to the study.

Amyloid protein is a sticky, globular substance created when normal cellular proteins become twisted and contorted into abnormal shapes. While amyloid formation has been associated with diseases like Alzheimer’s, Parkinson’s, and Huntington’s, scientists have puzzled over whether and how it actually kills cells and causes disease. To gain insight into this mysterious process, Lal and his research team examined the three-dimensional structure of several different proteins associated with these diseases. The researchers observed that all of the proteins folded into structures resembling ion channels, or pores within cell membranes. These pores control the electrical properties of the cell by regulating the flow of charged particles (ions) such as calcium.

When embedded into artificial membranes, the misfolded proteins were able to produce electrical currents, confirming their similarity to ion channels. Since abnormal ion balance is known to disrupt cell function and cause degeneration, these results provide proof of a possible mechanism by which amyloid formation may lead to the cellular destruction seen in these neurodegenerative diseases.

"These ion channels could serve as a model system for designing preventive and therapeutic drugs," said Lal. "You don’t need large aggregates of these amyloid proteins, the plaque, to have this disruption. Rather, small aggregates, when in contact with membrane, form ion channels and allow passage of ion current. By controlling activity and designing specific drugs to regulate these channels, we might be able to prevent and/or treat various diseases related to the amyloids."

These findings provide a major piece of the puzzle about the underlying protein misfolding associated with these degenerative diseases. Besides the diseases already mentioned, other degenerative diseases that also result from misfolded proteins include cystic fibrosis, type II diabetes, cerebrovascular dementia, arthritis, tuberculosis, as well as British and Danish famial dementias.

The researchers used atomic force microscopy (AFM) to view the ion channels. By using the AFM they were able to view these "bio-nano" molecules. The AFM allows for a look at these very small channels, which would be very difficult if not impossible to see in their native, cell-like environment with electron microscopy.

In addition to Lal, the authors of this path-breaking paper are: Arjan Quist and Ivo Doudevski of the NRI at UCSB; Han Lin of the University of Pittsburgh; Rushana Azimova and Bruce Kagan of the University of California, Los Angeles; and Douglas Ng, Blas Frangione, and Jorge Ghiso of New York University.

Gail Gallessich | EurekAlert!
Further information:
http://www.ucsb.edu

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Spider silk key to new bone-fixing composite

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.

Im Focus: Writing and deleting magnets with lasers

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...

Im Focus: Gamma-ray flashes from plasma filaments

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...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

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...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>