Navigation Links
Kentucky study advances new target for CNS drug development
Date:1/15/2010

LEXINGTON, Ky. (Jan. 15, 2010) A breakthrough discovery by scientists at the University of Kentucky could someday lead to new treatments for a variety of diseases of the brain, spinal cord and the eye.

Researchers led by Royce Mohan, associate professor of ophthalmology and visual science in the UK College of Medicine, found that the small molecule withaferin A can simultaneously target two key proteins vimentin and glial fibrillary acidic protein (GFAP) implicated in a damaging biological process called reactive gliosis.

Both vimentin and GFAP, members of a family of proteins called intermediate filaments, are important factors in the stress response of the central nervous system (CNS). But pathology in the CNS from a traumatic injury or neurodegenerative disease can cause overexpression of vimentin and GFAP and lead to reactive gliosis.

During gliosis, astrocyte cells that express vimentin and GFAP accumulate into dense, fibrous patches called glial scars, which interfere with normal functioning of the CNS. Gliosis is a significant feature of many disorders of the CNS, including multiple sclerosis, Alzheimer's disease, stroke, and traumatic brain and spinal cord injury, and it is also central to major retinal diseases such as age-related macular degeneration, diabetic retinopathy and glaucoma.

Mohan's lab discovered that withaferin A binds to both vimentin and GFAP within an unique pocket when these proteins are in their soluble, tetrameric form. This finding makes withaferin A an appealing therapeutic lead for drug-development research, Mohan said, and he owes great credit to the interdisciplinary team of collaborators who contributed to extending this finding.

Mohan describes the discovery as serendipitous. Originally, his team was investigating withaferin A as an angiogenesis inhibitor, a type of drug used to slow the development and growth of new blood vessels. Such drugs are useful in treating cancers and various conditions of the eye, such as corneal neovascularization, wet-stage macular degeneration and glaucoma.

Using an approach called reverse chemical genetics, Mohan's lab started with the identification of withaferin A as a vimentin probe, and then looked for CNS pathological indications where the related type III intermediate filament GFAP is critically involved.

"It was fortuitous that we looked at the retina of injured mice," Mohan said. "This drug was causing simultaneous inhibition of both corneal angiogenesis and retinal gliosis, a finding that is relevant to combat ocular trauma from the alarming incidence of blast injuries. Rarely does one get the opportunity to make an important discovery that advances on two drug targets at once."


'/>"/>

Contact: Keith Hautala
keith.hautala@uky.edu
859-323-6363
University of Kentucky
Source:Eurekalert

Related biology news :

1. $2M grant awarded to University of Kentucky for research on nanoparticles and human health
2. National scientific meeting on child mental health at Kentucky
3. BIO-key(R) Awarded Mobile Data Contract for Additional 10 Kentucky Law Enforcement Agencies
4. New study suggests minke whales are not preventing recovery of larger whales
5. You say offset, I say tax? Study suggests labels and political affiliation may affect preferences
6. Study shows pine bark naturally relieves symptoms of acute hemorrhoids
7. Study shows that delivering stem cells improves repair of major bone injuries in rats
8. Study reveals how one form of natural vitamin E protects brain after stroke
9. What came first in the origin of life? A study contradicts the metabolism first hypothesis
10. Study examines calorie information from restaurants, packaged foods
11. Study provides insight into pathway linked to obesity
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... -- First quarter 2016:   , Revenues ... first quarter of 2015 The gross margin was 49% ... and the operating margin was 40% (-13) Earnings per ... from operations was SEK 249.9 M (21.2) , Outlook ... 7,000-8,500 M. The operating margin for 2016 is estimated ...
(Date:4/15/2016)... DUBLIN , April 15, 2016 ... of the,  "Global Gait Biometrics Market 2016-2020,"  report ... http://photos.prnewswire.com/prnh/20160330/349511LOGO ) , ,The global gait ... CAGR of 13.98% during the period 2016-2020. ... movement angles, which can be used to compute ...
(Date:3/29/2016)... , March 29, 2016 ... "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are pleased to ... ink used in a variety of writing instruments, ensuring ... of originally created collectibles from athletes on LegacyXChange will ... analysis of the DNA. Bill Bollander ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... Bangkok, Thailand (PRWEB) , ... May 25, 2016 ... ... the participation of a Thai delegation at BIO 2016 in San Francisco. Located ... private sector will be available to answer questions and discuss the Thai biotechnology ...
(Date:5/25/2016)... ... May 25, 2016 , ... WEDI, the nation’s leading authority on the use ... W. Stellar has been named by the WEDI Board of Directors as WEDI’s president ... executive leader with more than 35 years of experience in healthcare, association management and ...
(Date:5/24/2016)... La Jolla, CA (PRWEB) , ... May 24, 2016 , ... ... and financial planning for corporate executives and entrepreneurs, held The Future of San Diego ... leaders in the San Diego life science community attended the event with speakers Dr. ...
(Date:5/23/2016)... 23, 2016 Oxitec CEO Hadyn ... at 10:15 a.m. ET before the United States House Committee ... mosquitos can play in controlling the spread of the ... virus.      (Logo: http://photos.prnewswire.com/prnh/20150630/227348 ) ... a self-limiting gene. Trials in Brazil , ...
Breaking Biology Technology: