Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New study uncovers how cellular stress causes brain damage

15.12.2010
Researchers at RIKEN have linked a specific type of cellular stress to neuronal cell death leading to brain damage. The findings overturn existing assumptions on the role of a key neuronal protein in cellular stress response, opening up new avenues for research on a range of neurodegenerative diseases.

New findings by researchers at RIKEN, Japan’s flagship research institution, have linked a specific type of cellular stress to neuronal cell death leading to brain damage. Published in the journal Neuron, the findings overturn existing assumptions on the role of a key neuronal protein in cellular stress response, opening up new avenues for research on a range of neurodegenerative diseases.

As an organelle responsible for the production, processing and transport of a wide variety of cellular materials, the endoplasmic reticulum (ER) plays a central role in maintaining protein quality in the cell. Pathological conditions that affect protein folding or calcium signaling can interfere with this role, causing stress to the ER which, in severe cases, can trigger cell death (apoptosis). In the brain, such apoptosis has been associated with neurodegenerative diseases such as Alzheimer’s disease and Huntington’s disease (HD), yet the mechanisms involved remain poorly understood.

To clarify these mechanisms, the researchers investigated the relationship between ER stress and a neuronal protein called inositol 1,4,5-trisphosphate receptor 1 (IP3R1), one of three IP3R receptors that modulate intracellular calcium signaling. Using calcium imaging techniques, the team identified a sharp decline in IP3R1 activity in cells treated with ER stress inducers. It was further revealed that the ER stress-dependent dysfunction of IP3R1 induced neuronal cell death and brain damage, situating IP3R1 as a crucial link between ER stress and neuron cell death.

Underlying this link, the researchers identified a mechanism through which GRP78, a molecular chaperone, binds to a region of IP3R1 called L3V to positively regulate tetrameric assembly of IP3R1. ER stress, they show, impairs this assembly mechanism and subsequently inhibits IP3R1 activation, a process also observed in the brain of model mice with HD.

As the first research to highlight the significant role of IP3R1 in protecting the brain from ER stress, the Neuron study marks a major step toward clarifying the mechanisms underlying stress-induced brain damage, promising advancements in the treatment of neurodegenerative diseases.

For more information, please contact:

Dr. Katsuhiko Mikoshiba
Laboratory for Developmental Neurobiology
RIKEN Brain Science Institute
Tel: +81-(0)48-467-9745 / Fax: +81-(0)48-467-9744
Ms. Tomoko Ikawa (PI officer)
Global Relations Office
RIKEN
Tel: +81-(0)48-462-1225 / Fax: +81-(0)48-463-3687
Email: koho@riken.jp
Reference:
Takayasu Higo, Kozo Hamada, Chihiro Hisatsune, Nobuyuki Nukina, Tsutomu Hashikawa, Mitsuharu Hattori, Takeshi Nakamura and Katsuhiko Mikoshiba. Mechanism of ER Stress-Induced Brain Damage by IP3 Receptor. Neuron 68(5): 865-878. DOI: 10.1016/j.neuron.2010.11.010

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

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

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>