Navigation Links
Targeting PARP1 Is Effective In Protecting HD Cells from Damage

According to a study conducted by the researchers at the MassGeneral Institute for Neurodegenerative Disease (MIND) it was found that inhibitor of an enzyme known as Poly //(ADP-ribose) polymerase (PARP1) is very effective in protecting Huntington’s disease affected cells from undergoing damage.

By targeting this enzyme new drugs can be developed to treat Huntington's disease (HD) and other disorders characterized by low cellular energy levels. The study results are published in the journal of Chemistry & Biology. ‘While PARP1 is essential for the repair of damaged DNA, we also know that, if overactivated, it can cause cell death by excessive energy depletion,’ says Aleksey Kazantsev, PhD, director of the MIND High Throughput Drug Screening Laboratory, who led the current study. ‘It has recently been shown that neurons from patients with Huntington's appear to be energy-deficient, so we hypothesized that modest stresses that would be tolerated by healthy cells could send HD cells below a viable energy threshold and that blocking PARP1 activation could be protective.’

To test this hypothesis the MIND researchers first ran a computer search of their small-molecule library for potential novel inhibitors of PARP1, searching for those with structural similarities to known inhibitors. ‘Safety and efficacy of human drugs depends on many factors, so it's hard to predict which inhibitor would be most effective against a specific disorder. The more diverse novel inhibitors can be identified, the more chances there are of developing safe and effective drugs,’ Kazantsev explains.

Two candidate molecules were identified as potential PARP1 inhibitors based on their structure, and both of them were confirmed to inhibit the enzyme's activity in an in vitro assay. However, when tested using cultured human and rat cells, only one of the candidate molecules, K245-14, successfully prevented the death of cells in which PARP1 had been overactivated. The nex t assays examined whether blocking PARP1 activity with K245-14 could reduce energy depletion in cells with the HD genetic mutation. Using cells from human HD patients and from a mouse model of the disorder, the MIND researchers compared the reactions of HD cells to oxidative stress caused by the application of hydrogen peroxide with the reactions of normal cells.

Although all of the cells reacted with a loss of ATP, a key source of cellular energy, the HD cells – which had much lower ATP levels to begin with – were much more vulnerable to stress-induced energy loss. Inhibiting PARP1 by means of K245-14 reduced ATP loss in all tested cells and significantly protected against both energy loss and cell death in the HD cells. ‘While we were pleased to observe these predicted protective effects in our experiments, validation of PARP1 as a useful HD drug target will require the testing of inhibitors in animal trials,’ Kazantsev explains.

The process of identifying the best candidates for trials will be very complex, since any drug treating a central nervous system disorder needs to penetrate the blood-brain barrier. We will be working with our collaborators at the Scripps Research Institute – world leaders in computational chemistry – to conduct a more comprehensive virtual screen and select additional promising candidates for drug development. ‘Inhibition of PARP1 activity is thought to be potentially beneficial for treatment of cancer, neurodegenerative conditions such as Parkinson's disease, and over twenty other human disorders,’ he adds. ‘We envision broad therapeutic applications for small molecule inhibitors of PARP1.’ Kazantsev is an assistant professor of Neurology at Harvard Medical School.

Souce: Eurekalert
'"/>




Related medicine news :

1. Novel Technique For Targeting Small-Cell Lung Cancer
2. Ad Campaign Targeting Republicans On Medicare Prescription Drug Program
3. By Targeting Specific Germs, Hospital Hopes to Improve Pneumonia Treatment
4. Highly Potent TB Strain Plays Favorites Targeting Specific Ethnic Groups
5. New Asthma Medicine Targeting Vulnerable Inner-City Children Tested
6. Targeting a Single Gene Could Inhibit Bone Decay and Stimulate Bone Growth
7. Researchers Find Stem-cell Therapy Effective in Targeting Metastatic Cancer
8. Targeting the Adrenal Gland Could Be Key Against Heart Failure
9. Targeting SOCS-3 can Control Obesity
10. Sex Abstinence Programs Targeting School-goers may Not Produce Desired Effect , Study
11. New Way to "See" Genes, Evaluate Effectiveness of Gene Therapies Discovered
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is World ... with chronic pain and the benefits of holistic treatments, Serenity Recovery Center ... with Sickle Cell Disease. , Sickle Cell Disease (SCD) is a disorder of the ...
(Date:6/24/2016)... ... June 24, 2016 , ... Global law firm Greenberg Traurig, ... Elite. The attorneys chosen by their peers for this recognition are considered among the ... Traurig Shareholders received special honors as members of this year’s Legal Elite Hall of ...
(Date:6/24/2016)... ... ... Inc, makers of Topricin and MyPainAway Pain Relief Products, join The ‘Business for a Fair ... hour by 2020 and then adjusting it yearly to increase at the same rate as ... the wage floor does not erode again, and make future increases more predictable. , The ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... Living, is proud to recognize Dr. Barry M. Weintraub as a prominent plastic ... most beautiful women in the world, and the most handsome men, look naturally ...
(Date:6/24/2016)... ... , ... National recruitment firm Slone Partners is pleased to announce ... experience, as Vice President of North American Capital Sales at HTG Molecular . ... sales team in the commercialization of the HTG EdgeSeq system and associated reagents in ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... 2016   Bay Area Lyme Foundation , ... Center for Tick Borne Illness , Harvard Medical ... Hacking Medicine, University of California, Berkeley, and the ... five finalists of Lyme Innovation , the ... 100 scientists, clinicians, researchers, entrepreneurs, and investors from ...
(Date:6/24/2016)... , June 24, 2016  American Respiratory Labs (ARL), a ... now able to perform sophisticated lung assessments in patients, homes, thanks ... Inc. Patients are no longer limited to having ... PRO ® , ARL patients like Jeanne R. of ... the comfort of her own home. ...
(Date:6/24/2016)... , June 24, 2016  Arkis BioSciences, a ... invasive and more durable cerebrospinal fluid treatments, today ... The Series-A funding is led by Innova Memphis, ... and other private investors.  Arkis, new financing will ... and the market release of its in-licensed Endexo® ...
Breaking Medicine Technology: