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 Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

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

Microhotplates for a smart gas sensor

22.02.2017 | Power and Electrical Engineering

Scientists unlock ability to generate new sensory hair cells

22.02.2017 | Life Sciences

Prediction: More gas-giants will be found orbiting Sun-like stars

22.02.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>