Featured Research

from universities, journals, and other organizations

Brain development: Researchers identify key protein

Date:
January 22, 2014
Source:
Medical University of Vienna
Summary:
A group of proteins has been on the watch list of scientists because of their important function in epigenetics: histone deacetylases coordinate the transcription of genetic information and play an important role in the development of diseases such as cancer and neurodegenerative disorders. Researchers recently demonstrated that deactivating HDAC1 accelerates skin tumor development – a vital finding that has to be taken into account when developing new drugs to treat skin tumors.

Scientists from the Max F. Perutz Laboratories (MFPL) of the University of Vienna and the Medical University of Vienna have identified a specific enzyme, histone deacetylase 2 (HDAC2), as essential for brain development. The findings published in Development are important to advance the development of new drugs to treat neurological diseases.

A group of proteins, the histone deacetylases (HDACs), have been on the watch list of scientists worldwide for more than two decades. This attention is owed to their important function in epigenetics: histone deacetylases coordinate the transcription of genetic information and play an important role in the development of diseases such as cancer and neurodegenerative disorders.

HDACs inhibitors have already been applied therapeutically. However, recent studies show that the 18 variants of HDACs known in humans have individual roles in different cell types. Christian Seiser and his team at the Max F. Perutz Laboratories (MFPL) of the Medical University of Vienna, for example, recently demonstrated that deactivating HDAC1 actually accelerates skin tumor development -- a vital finding that has to be taken into account when developing new drugs to treat skin tumors.

HDAC2 is crucial for survival

In their new study supported by the Austrian Genome research program GEN-AU and the FWF Christian Seiser and his team show that HDAC2 plays a key role in brain development. They investigated the function of the homologs HDAC1 and HDAC2, which have overlapping functions, by completely or partly ablating these enzymes. These two variants had already shown to be important for the development of a normal brain structure during embryogenesis. Indeed, mice did not survive the embryonic stage when both HDAC1 and HDAC2 were completely ablated.

However, in the following experiments it became clear that HDAC2 plays the crucial role in brain development: When HDAC2 function was only partly and HDAC1 function completely ablated, the organisms were viable and fertile. While vice versa, when HDAC2 function was totally and HDAC1 function only partly ablated, the offspring died within one day after birth. These mice were also found to have excessive levels of an enzyme called protein kinase C delta -- later shown to be the reason for the impaired proliferation of progenitor cells into brain cells.

"The neonatal brain is smaller and shows less cell proliferation," explains first author Astrid Hagelkruys, who had successfully defended her PhD just a few days after the paper was accepted by Development. It is still unclear why the offspring die shortly after birth. It is possible that the occurring neurological defects influence, for example, coordination and olfactory recognition which may make the newborns unable to find the way to the mother who could provide them with food.

The impaired cell proliferation and differentiation could be restored by inhibiting or deactivating protein kinase C delta. This data indicates that HDAC2 plays a unique role in controlling cell fate during brain development by regulating key factors such as protein kinase C delta.

Results are important for the development of neurotherapeutic drugs HDAC inhibitors have shown beneficial effects in animal models for the treatment of Alzheimer's disease and Parkinson's disease and they are already approved for the treatment of epilepsy in humans. The results of the scientists from the MFPL may help the development of specific drugs to ameliorate brain function.


Story Source:

The above story is based on materials provided by Medical University of Vienna. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. Hagelkruys, S. Lagger, J. Krahmer, A. Leopoldi, M. Artaker, O. Pusch, J. Zezula, S. Weissmann, Y. Xie, C. Schofer, M. Schlederer, G. Brosch, P. Matthias, J. Selfridge, H. Lassmann, J. A. Knoblich, C. Seiser. A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog. Development, 2014; 141 (3): 604 DOI: 10.1242/dev.100487

Cite This Page:

Medical University of Vienna. "Brain development: Researchers identify key protein." ScienceDaily. ScienceDaily, 22 January 2014. <www.sciencedaily.com/releases/2014/01/140122091453.htm>.
Medical University of Vienna. (2014, January 22). Brain development: Researchers identify key protein. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2014/01/140122091453.htm
Medical University of Vienna. "Brain development: Researchers identify key protein." ScienceDaily. www.sciencedaily.com/releases/2014/01/140122091453.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
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:
from the past week

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