Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study Advances New Target for CNS Drug Development

19.01.2010
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."

This research was supported by grants from the National Institutes of Health, the RPB Foundation and the Kentucky Science and Technology Corporation. The study, "Withaferin A Targets Intermediate Filaments GFAP and Vimentin in a Model of Retinal Gliosis," was published online Jan. 4 in the Journal of Biological Chemistry, with senior scientist Paola Bargagna-Mohan as lead author. Additional authors are: Riya R. Paranthan, Adel Hamza, Neviana Dimova, Beatrice Trucchi, Cidambi Srinivasan, Gregory I. Elliott, Chang-Guo Zhan, Daniel L. Lau, Haiyan Zhu, Kousuke Kasahara, Masaki Inagaki, Franca Cambi and Royce Mohan.

Keith Hautala | Newswise Science News
Further information:
http://www.uky.edu

Further reports about: Advance CNS Drug Delivery End User Development GFAP Gliosis Kentucky Mohan Target blood vessel key protein

More articles from Studies and Analyses:

nachricht Study relating to materials testing Detecting damages in non-magnetic steel through magnetism
23.07.2018 | Technische Universität Kaiserslautern

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>