Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Calcium aids protein folding as therapy for enzymes in types of lysosomal storage diseases

05.02.2008
Lysosomes are organelles that break down macromolecules in a cell, and this process is crucial for maintaining healthy cells. A lysosomal storage disease results from deficient activity of the hydrolytic enzymes, responsible for the breakdown of defunct molecules.

Currently, lysosomal storage diseases are treated by enzyme replacement therapy. This can be challenging because the enzyme has to find its proper way into cells and lysosomes to function. In neuropathic diseases, enzyme replacement is not useful because recombinant enzymes do not enter the brain.

This week in the open-access online journal PLoS Biology, Tingwei Mu, Douglas Fowler, and Jeffrey Kelly show that diltiazem and verapamil, potent FDA approved L-type Ca2+ channel blocking drugs, could restore the activity of mutant lysosomal enzymes associated with three distinct lysosomal storage diseases. The drugs acted by increasing the endoplasmic reticulum (ER) folding capacity and trafficking.

These compounds appear to function through a Ca2+ ion-mediated upregulation of a subset of cytoplasmic and ER lumenal chaperones, possibly by activating signaling pathways that lessen cellular stress. They have shown that increasing ER calcium levels appears to be a relatively selective strategy to partially restore mutant lysosomal enzyme homeostasis in diseases caused by the misfolding and degradation of mutant enzymes. Since diltiazem crosses the blood-brain barrier, it may be useful for the treatment of neuropathic lysosomal storage diseases, and possibly other loss-of-function diseases, although efficacy needs to be demonstrated before this happens.

... more about:
»Mutant »Storage »enzyme »lysosomal

Citation: Mu TW, Fowler DM, Kelly JW (2008) Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis PLoS Biol 6(2): e26. doi:10.1371/journal.pbio.0060026

CONTACT:
Jeffrey Kelly
Scripps Research Institute
The Skaggs Institute for Chemical Biology
10550 North Torrey Pines Road
La Jolla, CA 92037
United States of America
+1-858-784-9605
+1-858-784-9610 (fax)
jkelly@scripps.edu

Natalie Bouaravong | EurekAlert!
Further information:
http://www.plosbiology.org

Further reports about: Mutant Storage enzyme lysosomal

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>