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:

(Date:10/13/2017)... ... , ... PurhealthRX , a leading Health and Nutrition Company, is announcing ... full spectrum CBD oil will revolutionize the rapidly growing CBD market by reducing the ... incorporated into liquid products, while reducing costs to end users. , The team of ...
(Date:10/13/2017)... ... 13, 2017 , ... Lori R. Somekh, founder of the Law Office ... of elder law and special needs planning attorneys. “Membership in ElderCounsel helps our office ... forum to network with elder law attorneys nationwide,” said Somekh. , ElderCounsel ...
(Date:10/13/2017)... ... October 13, 2017 , ... Many families have long-term insurance ... care insurance companies have a waiver for care if the client has a cognitive ... the family pays for care, is often waived, so the benefits from their insurance ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Ellevate Network, the ... business to advocate for action towards gender equality at their inaugural Summit in New ... the globe, and reached a social audience of over 3 million. To watch the ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer at ... of the most popular and least understood books in the Holy Scriptures, Revelation. The ... that have baffled scholars for centuries. Many have tossed it off as mere rubbish, ...
Breaking Medicine News(10 mins):
(Date:9/27/2017)... NEW YORK , Sept. 27, 2017  DarioHealth Corp. (NASDAQ: DRIO), ... solutions, today announced that its MyDario product is expected to appear on ... for when The Dr. Oz Show airs in your area: ... The nine-time Emmy award-winning, The Dr. ... ...
(Date:9/22/2017)... , Sept. 22, 2017 AVACEN Medical (AVACEN) ... is now successfully helping those with the widespread pain ... Fibromyalgia diagnosed Amanda in Essex, England ... washing my hair, experiencing no sleep at all, tremendous ... spasm… I cannot recommend [the AVACEN 100] enough, how ...
(Date:9/13/2017)... has been named the official orthopedic and sports medicine ... 2018 College Football Playoff (CFP) National Championship to be played ... Atlanta, Georgia . OrthoAtlanta is proud to be ... many activities leading up to, and including the national championship ... OrthoAtlanta serves ...
Breaking Medicine Technology: