Navigation Links
Proteasome activator enhances survival of Huntington's disease neuronal model cells

To function, each living cell needs both to build new and to degrade old or damaged proteins. To accomplish that, a number of intracellular systems work in concert to keep the cell healthy and from clogging up with damaged proteins. When proteins or peptides mutate, they can present major problems to the clearing up of the intracellular environment. In Huntington's disease (HD) the disease provoking mutation in the huntingtin gene eventually causes the cell to build up intranuclear and cellular inclusions of protein-aggregates, made up primarily of huntingtin. One cellular organelle with a central role of clearing such protein build up in the cell is the ubiquitin proteasome system (UPS).

In Huntington's disease (HD) brains and other tissues, UPS activity is inhibited and intraneuronal nuclear protein aggregates of mutant huntingtin in HD brains indicate dysfunction of the UPS. From these results, we hypothesized that enhancing UPS function would improve catalytic degradation of abnormal proteins in HD. We first genetically engineered proteasome activators involved in either non-ubiquitinated protein degradation pathways (PA28ƒ×) or subunits of PA700, the 26S proteasome ubiquitinated pathway (S5a) into transducible lentiviral vectors. To address the therapeutic hypothesis experimentally, we transduced UPS subunits into HD skin fibroblasts or HD mutant protein expressing striatum-derived neurons. We determined how this intervention altered cell survival after exposure to toxins known to simulate pathological mechanisms in HD.

The manuscript shows that cellular changes due to expression of huntingtin protein with longer CAG repeats can reduce the ubiquitin proteasome system (UPS) function in Huntington¡¦s disease cells. Following compromise of the UPS, the overexpression of proteasome activator PA28 can specifically recover proteasome function and improve cell viability in both HD model and patient cells.

These remarkable results demonstrat e for the first time that it is possible to intervene therapeutically in the proteolytic pathways and organelles that participate in the specific degradation of misfolded and abnormal proteins.


'"/>

Source:Public Library of Science


Related biology news :

1. Pulsating ultrasound enhances gene therapy for tumors
2. Elevated temperature enhances success of viral cancer therapy
3. NYU algorithm enhances ability to detect cancer genes
4. The Bacterias guide to survival
5. Boosting HIV screening can increase survival and is cost effective
6. Researchers identify protein crucial for survival of Lyme-disease bacterium
7. Novel protein complex enables survival in hostile environment
8. BiovaxID?yields 89 percent survival in patients with aggressive non-Hodgkins
9. UCI researchers discover key factor for survival of human embryonic stem cells
10. Rhinos clinging to survival in the heart of Borneo, despite poaching
11. DNA: Bacterias survival ration
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/31/2016)... Florida , March 31, 2016 ... ) ("LegacyXChange" or the "Company") LegacyXChange ... potential users of its soon to be launched online ... ( https://www.youtube.com/channel/UCyTLBzmZogV1y2D6bDkBX5g ) will also provide potential ... use of DNA technology to an industry that is ...
(Date:3/29/2016)... , March 29, 2016 LegacyXChange, ... LegacyXChange "LEGX" and SelectaDNA/CSI Protect are pleased to announce ... used in a variety of writing instruments, ensuring athletes ... originally created collectibles from athletes on LegacyXChange will be ... of the DNA. Bill Bollander , ...
(Date:3/22/2016)... PUNE, India , March 22, 2016 ... new market research report "Electronic Sensors Market for ... Fingerprint, Proximity, & Others), Application (Communication & ... and Geography - Global Forecast to 2022", ... consumer industry is expected to reach USD ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... ... May 25, 2016 , ... WEDI, the nation’s leading authority on ... that Charles W. Stellar has been named by the WEDI Board of Directors as ... As an executive leader with more than 35 years of experience in healthcare, association ...
(Date:5/25/2016)... ... May 25, 2016 , ... Biohaven Pharmaceutical Holding Company Ltd. ... the company’s orphan drug designation request covering BHV-4157 for the treatment of Spinocerebellar ... FDA. , Spinocerebellar ataxia is a rare, debilitating neurodegenerative disorder that is ...
(Date:5/24/2016)... , May 24, 2016   MedyMatch Technology Ltd ... with artificial intelligence, real-time decision support tools in the emergency ... at the 2016 Israeli Advanced Technology Industries (IATI) BioMed Conference. ... Israel,s 15th National Life Sciences and Technology ... the David Intercontinental Hotel in Tel Aviv, Israel ...
(Date:5/24/2016)... ... 24, 2016 , ... Media Cybernetics, global image analysis leader, ... branding reflects a results-driven revitalization for a company with a renewed focus on ... a crisp, refreshed logo and a new web presence. , “I believe that ...
Breaking Biology Technology: