Featured Research

from universities, journals, and other organizations

Molecular 'scaffold' could hold key to new dementia treatments

Date:
June 3, 2014
Source:
King's College London
Summary:
A molecular 'scaffold' that allows key parts of cells to interact appears to come apart in dementia and motor neuron disease, revealing a potential new target for drug discovery, researchers report. Researchers looked at two components of cells: mitochondria, and the endoplasmic reticulum (ER). ER and mitochondria form close associations and these interactions enable a number of important cell functions. However the mechanism by which ER and mitochondria become linked has not, until now, been fully understood.

Researchers at King's College London have discovered how a molecular 'scaffold' which allows key parts of cells to interact, comes apart in dementia and motor neuron disease, revealing a potential new target for drug discovery.

The study, published today in Nature Communications, was funded by the UK Medical Research Council, Wellcome Trust, Alzheimer's Research UK and the Motor Neurone Disease Association.

Researchers looked at two components of cells: mitochondria, the cell 'power houses' which produce energy for the cell; and the endoplasmic reticulum (ER) which makes proteins and stores calcium for signalling processes in the cell. ER and mitochondria form close associations and these interactions enable a number of important cell functions. However the mechanism by which ER and mitochondria become linked has not, until now, been fully understood.

Professor Chris Miller, from the Institute of Psychiatry at King's and lead author of the paper, says: "At the molecular level, many processes go wrong in dementia and motor neuron disease, and one of the puzzles we're faced with is whether there is a common pathway connecting these different processes. Our study suggests that the loosening of this 'scaffold' between the mitochondria and ER in the cell may be a key process in neurodegenerative diseases such as dementia or motor neuron disease."

By studying cells in a dish, the researchers discovered that an ER protein called VAPB binds to a mitochondrial protein called PTPIP51, to form a 'scaffold' enabling ER and mitochondria to form close associations. In fact, by increasing the levels of VAPB and PTPIP51, mitochondria and ER re-organised themselves to form tighter bonds.

Many of the cell's functions that are controlled by ER-mitochondria associations are disrupted in neurodegenerative diseases, so the researchers studied how the strength of this 'scaffold' was affected in these diseases. TPD-43 is a protein which is strongly linked to Amyotrophic Lateral Sclerosis (ALS, a form of motor neuron disease) and Fronto-Temporal Dementia (FTD, the second most common form of dementia), but exactly how the protein causes neurodegeneration is not properly understood.

The researchers studied how TPD-43 affected mouse cells in a dish. They found that higher levels of TPD-43 resulted in a loosening of the scaffold which reduced ER-mitochondria bonds, affecting some important cellular functions that are linked to ALS and FTD.

Professor Miller concludes: "Our findings are important in terms of advancing our understanding of basic biology, but may also provide a potential new target for developing new treatments for these devastating disorders."


Story Source:

The above story is based on materials provided by King's College London. Note: Materials may be edited for content and length.


Journal Reference:

  1. Radu Stoica, Kurt J. De Vos, Sιbastien Paillusson, Sarah Mueller, Rosa M. Sancho, Kwok-Fai Lau, Gema Vizcay-Barrena, Wen-Lang Lin, Ya-Fei Xu, Jada Lewis, Dennis W. Dickson, Leonard Petrucelli, Jacqueline C. Mitchell, Christopher E. Shaw, Christopher C. J. Miller. ER–mitochondria associations are regulated by the VAPB–PTPIP51 interaction and are disrupted by ALS/FTD-associated TDP-43. Nature Communications, 2014; 5 DOI: 10.1038/ncomms4996

Cite This Page:

King's College London. "Molecular 'scaffold' could hold key to new dementia treatments." ScienceDaily. ScienceDaily, 3 June 2014. <www.sciencedaily.com/releases/2014/06/140603092430.htm>.
King's College London. (2014, June 3). Molecular 'scaffold' could hold key to new dementia treatments. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2014/06/140603092430.htm
King's College London. "Molecular 'scaffold' could hold key to new dementia treatments." ScienceDaily. www.sciencedaily.com/releases/2014/06/140603092430.htm (accessed October 21, 2014).

Share This



More Health & Medicine News

Tuesday, October 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) — The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) — An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) — Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
CDC Calls for New Ebola Safety Guidelines

CDC Calls for New Ebola Safety Guidelines

AP (Oct. 20, 2014) — Centers for Disease Control and Prevention Director Dr. Tom Frieden laid out new guidelines for health care workers when dealing with the deadly Ebola virus including new precautions when taking off personal protective equipment. (Oct. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins