Unraveling Batten disease

Nov 02, 2011

Waste management is a big issue anywhere, but at the cellular level it can be a matter of life and death. A Weizmann Institute study, published in the Journal of Cell Biology, has revealed what causes a molecular waste container in the cell to overflow in Batten disease, a rare but fatal neurodegenerative disorder that begins in childhood. The findings may form the basis for a therapy for this disorder.

In Batten disease, an insoluble yellow pigment accumulates in the brain's , causing these cells to degenerate and ultimately die. Patients gradually become disabled, losing their vision and motor skills and suffering mental impairment; they rarely survive beyond their early twenties. It's been known for a while that the disorder is caused by a mutation in the gene referred to as CLN3, but the role of this gene in the cell was unknown. This role has now been discovered in the Weizmann Institute study, explaining the molecular dysfunction in Batten disease.

The research was conducted in the laboratory of Prof. Jeffrey Gerst of the Molecular Genetics Department by Rachel Kama and postdoctoral fellow Dr. Vydehi Kanneganti, in collaboration with Prof. Christian Ungermann of the University of Osnabrueck in Germany. All the studies were performed in yeast: The yeast equivalent of the mammalian CLN3 gene has been conserved almost intact in the course of evolution, making them ideal models for study. In fact, so similar are the yeast and the mammalian genes that when the researchers replaced a missing copy of the with a working copy of mammalian CLN3, normal functioning of the yeast cell was restored.

The experiments showed that the yeast equivalent of CLN3 is involved in moving proteins about the cell – the scientific term is "protein trafficking." The gene activates an enzyme of the kinase family, which, in turn, launches a series of molecular events regulating the trafficking. When the yeast CLN3 is mutated, this trafficking is disrupted. As a result, certain proteins accumulate abnormally in the lysosome, the cell's waste-recycling machine, instead of being transported to another destination. At some point the lysosome is filled beyond capacity; it then interferes with molecular signaling and other vital processes in the neuron, eventually killing the cell.

A great deal of research must still be performed before this finding benefits humans, but the clarification of the CLN3 function is precisely what might help develop a new therapy. Replacing the defective CLN3 in all the brain's neurons is a daunting challenge, but replacing its function – for example, by activating the relevant kinase by means of a drug – should be much more feasible.

Explore further: Researchers discover new mechanism of DNA repair

Related Stories

Recommended for you

Researchers discover new mechanism of DNA repair

23 hours ago

The DNA molecule is chemically unstable giving rise to DNA lesions of different nature. That is why DNA damage detection, signaling and repair, collectively known as the DNA damage response, are needed.

Stopping Candida in its tracks

Jul 03, 2015

Scientists are one step closer to understanding how a normally harmless fungus changes to become a deadly infectious agent.

New technique maps elusive chemical markers on proteins

Jul 02, 2015

Unveiling how the 20,000 or so proteins in the human body work—and malfunction—is the key to understanding much of health and disease. Now, Salk researchers developed a new technique that allows scientists ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.