New mechanism links cellular stress and brain damage

December 08, 2010

A new study uncovers a mechanism linking a specific type of cellular stress with brain damage similar to that associated with neurodegenerative disease. The research, published by Cell Press in the December 9 issue of the journal Neuron, is the first to highlight the significance of the reduction of a specific calcium signal that is directly tied to cell fate.

Body cells are constantly exposed to various environmental stresses. Although cells possess some natural defenses, excessive stress can lead to a type of cell death called apoptosis. "It is thought that excessive stress impacts brain function by inducing neuronal apoptosis and may play a role in neurodegenerative diseases such as Alzheimer's disease and Huntington's disease (HD)," explains senior study author, Dr. Katsuhiko Mikoshiba, from the Laboratory for Developmental Neurobiology at RIKEN Brain Science Institute.

HD is also associated with abnormal calcium signaling and the accumulation of misfolded proteins. Altered function of an intracellular structure called the endoplasmic reticulum (ER) that plays a key role in protein "quality control" and is a critical regulator of intracellular calcium signaling has been implicated in HD pathogenesis, but the specific underlying mechanisms linking ER stress with calcium and apoptosis are poorly understood.

Dr. Mikoshiba and colleagues demonstrated that a neuronal protein called inositol 1,4,5-trisphosphate receptor 1 (IP3R1) which regulates cellular calcium signaling was destroyed by ER stress and subsequently induced neuronal cell death and brain damage. The researchers went on to show that a protective "chaperone" protein called GRP78 positively regulated IP3R1 and that ER stress led to an impaired IP3R1-GRP78 interaction, which has also been observed in an animal model of HD.

"Based on our observation that the functional interaction between IP3R1 and GRP78 is impaired during ER stress and in the HD model, we propose that IP3R1 functions to protect the brain against stress and that the linkage between ER stress, IP3/calcium signaling, and neuronal cell death are associated with neurodegenerative disease." concludes Dr. Mikoshiba.
-end-
For more research news published by Neuron, go to http://www.eurekalert.org/jrnls/cell/pages/neuron.php

Cell Press

Related Stress Articles from Brightsurf:

Stress-free gel
Researchers at The University of Tokyo studied a new mechanism of gelation using colloidal particles.

Early life stress is associated with youth-onset depression for some types of stress but not others
Examining the association between eight different types of early life stress (ELS) and youth-onset depression, a study in JAACAP, published by Elsevier, reports that individuals exposed to ELS were more likely to develop a major depressive disorder (MDD) in childhood or adolescence than individuals who had not been exposed to ELS.

Red light for stress
Researchers from the Institute of Industrial Science at The University of Tokyo have created a biphasic luminescent material that changes color when exposed to mechanical stress.

How do our cells respond to stress?
Molecular biologists reverse-engineer a complex cellular structure that is associated with neurodegenerative diseases such as ALS

How stress remodels the brain
Stress restructures the brain by halting the production of crucial ion channel proteins, according to research in mice recently published in JNeurosci.

Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.

How plants handle stress
Plants get stressed too. Drought or too much salt disrupt their physiology.

Stress in the powerhouse of the cell
University of Freiburg researchers discover a new principle -- how cells protect themselves from mitochondrial defects.

Measuring stress around cells
Tissues and organs in the human body are shaped through forces generated by cells, that push and pull, to ''sculpt'' biological structures.

Cellular stress at the movies
For the first time, biological imaging experts have used a custom fluorescence microscope and a novel antibody tagging tool to watch living cells undergoing stress.

Read More: Stress News and Stress Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.