Featured Research

from universities, journals, and other organizations

Discovery of new drug targets for memory impairment in Alzheimer's disease

Date:
July 9, 2014
Source:
Korea Institute of Science and Technology (KIST)
Summary:
Reactive astrocytes, which have been commonly observed in Alzheimer's patients, aberrantly and abundantly produce the chief inhibitory neurotransmitter GABA and release it through the Best1 channel, researchers have discovered. The released GABA strongly inhibits neighboring neurons to cause impairment in synaptic transmission, plasticity and memory. This discovery will open a new chapter in the development of new drugs for treating such diseases.

We are now a step closer to having a drug that can cure dementia and memory loss. Research team in Korea has discovered that reactive astrocytes, which have been commonly observed in Alzheimer's patients, aberrantly and abundantly produce the chief inhibitory neurotransmitter GABA and release it through the Best1 channel. The released GABA strongly inhibits neighboring neurons to cause impairment in synaptic transmission, plasticity and memory. This discovery will open a new chapter in the development of new drugs for treating such diseases.

Related Articles


The study led by Dr. C. Justin Lee at Korea Institute of Science and Technology (KIST) and Dr. Daesoo Kim(KAIST) is published of Nature Medicine on June 29 (Title: GABA from Reactive Astrocytes Impairs Memory in Mouse Models of Alzheimer Disease)

Alzheimer's disease, which is the most common cause of dementia, is fatal and currently, there is no cure. In Alzheimer's disease, brain cells are damaged and destroyed, leading to devastating memory loss. It is reported that 1 in 8 Americans aged 65 or over have Alzheimer's disease. In 2011, 7,600 elderly people with dementia lost their way back home and became homeless in Korea. However, to date, there has been no clear understanding of the mechanisms underlying dementia in Alzheimer's disease. So far, neuronal death is the only proposed mechanism available in scientific literature.

The research team discovered that reactive astrocytes in the brains of Alzheimer's disease model mice produce the inhibitory transmitter GABA by the enzyme Monoamine oxidase B(MAO-B) and release GABA through the Bestrophin-1 channel to suppress normal information flow during synaptic transmission. Based on this discovery, the team was able to reduce the production and release of GABA by inhibiting MAO-B or Bestrophin-1, and successfully ameliorate impairments in neuronal firing, synaptic transmission and memory in Alzheimer's disease model mice.

In the behavioral test, the team used the fact that mice tend to prefer dark places. If a mouse experiences an electric shock in a dark place, it will remember this event and avoid dark places from then on. However, a mouse with modeled Alzheimer's disease cannot remember if such shock is related to dark places and keeps going back to dark places. The team demonstrated that treating these mice with a MAO-B inhibitor fully recovered the mice's memory. The selegiline is currently used in Parkinson's disease as an adjunct therapy and considered as a one of best promising medicine for MAO-B inhibitor. But it has been previously shown to be less effective in Alzheimer's disease.

The team proved that selegiline is effective for a short time, but when it is used in long term, it loses its efficacy in Alzheimer's disease model mice. When treated for 1 week, selegiline brought the neuronal firing to a normal level. But when it was treated for 2 and 4 weeks, neuronal firing came back to the levels of untreated mice. From these results, the team proposed that there is a pressing need for a new drug that has long lasting effects.

Dr. C. Justin Lee said, "From this study, we reveal the novel mechanism of how Alzheimer's patients might lose their memory. We also propose new therapeutic targets, which include GABA production and release mechanisms in reactive astrocytes for treatment of Alzheimer's disease. Furthermore, we provide a stepping stone for the development of MAO-B inhibitors with long lasting efficacy."


Story Source:

The above story is based on materials provided by Korea Institute of Science and Technology (KIST). Note: Materials may be edited for content and length.


Journal Reference:

  1. Seonmi Jo, Oleg Yarishkin, Yu Jin Hwang, Ye Eun Chun, Mijeong Park, Dong Ho Woo, Jin Young Bae, Taekeun Kim, Jaekwang Lee, Heejung Chun, Hyun Jung Park, Da Yong Lee, Jinpyo Hong, Hye Yun Kim, Soo-Jin Oh, Seung Ju Park, Hyo Lee, Bo-Eun Yoon, YoungSoo Kim, Yong Jeong, Insop Shim, Yong Chul Bae, Jeiwon Cho, Neil W Kowall, Hoon Ryu, Eunmi Hwang, Daesoo Kim, C Justin Lee. GABA from reactive astrocytes impairs memory in mouse models of Alzheimer's disease. Nature Medicine, 2014; DOI: 10.1038/nm.3639

Cite This Page:

Korea Institute of Science and Technology (KIST). "Discovery of new drug targets for memory impairment in Alzheimer's disease." ScienceDaily. ScienceDaily, 9 July 2014. <www.sciencedaily.com/releases/2014/07/140709105053.htm>.
Korea Institute of Science and Technology (KIST). (2014, July 9). Discovery of new drug targets for memory impairment in Alzheimer's disease. ScienceDaily. Retrieved October 30, 2014 from www.sciencedaily.com/releases/2014/07/140709105053.htm
Korea Institute of Science and Technology (KIST). "Discovery of new drug targets for memory impairment in Alzheimer's disease." ScienceDaily. www.sciencedaily.com/releases/2014/07/140709105053.htm (accessed October 30, 2014).

Share This



More Health & Medicine News

Thursday, October 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Mind-Controlled Prosthetic Arm Restores Amputee Dexterity

Reuters - Innovations Video Online (Oct. 29, 2014) A Swedish amputee who became the first person to ever receive a brain controlled prosthetic arm is able to manipulate and handle delicate objects with an unprecedented level of dexterity. The device is connected directly to his bone, nerves and muscles, giving him the ability to control it with his thoughts. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Google To Use Nanoparticles, Wearables To Detect Disease

Google To Use Nanoparticles, Wearables To Detect Disease

Newsy (Oct. 29, 2014) Google X wants to improve modern medicine with nanoparticles and a wearable device. It's all an attempt to tackle disease detection and prevention. Video provided by Newsy
Powered by NewsLook.com
Can Drinking Milk Lead To Early Death?

Can Drinking Milk Lead To Early Death?

Newsy (Oct. 29, 2014) Researchers in Sweden released a study showing heavy milk drinkers face an increased mortality risk from a variety of causes. Video provided by Newsy
Powered by NewsLook.com
Obama: The US Will Not 'run and Hide' From Ebola

Obama: The US Will Not 'run and Hide' From Ebola

AP (Oct. 29, 2014) Surrounded by health care workers in the White House East Room, President Barack Obama said the U.S. will likely see additional Ebola cases in the weeks ahead. But he said the nation can't seal itself off in the fight against the disease. (Oct. 29) 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