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:2/2/2016)... , Feb. 2, 2016 This ... the bioinformatic market by reviewing the recent advances ... tools that drive the field forward. Includes forecast ... Identify the challenges and opportunities that exist ... and software solution developers, as well as IT ...
(Date:2/2/2016)... MOUNTAIN VIEW, Calif. , Feb. 2, 2016 ... diabetic retinopathy market, Frost & Sullivan recognizes US-based ... North America Frost & Sullivan Award for New ... technology provider in North America ... standard in the rapidly growing diabetic retinopathy market. ...
(Date:1/28/2016)... -- Synaptics (NASDAQ: SYNA ), a leading developer of human ... December 31, 2015. --> --> ... 2 percent compared to the comparable quarter last year to $470.5 ... $35.0 million, or $0.93 per diluted share. ... quarter of fiscal 2016 grew 9 percent over the prior year ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... International, a not-for-profit organization focused on the ethics and governance ... to patients around the world, today announced that the editors ... the Good Pharma Scorecard an ,Editors, Pick, ... of BMJ Open ,s ,Most Popular Articles, which includes ... read. Ed Sucksmith , assistant editor of ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... focused on the development and manufacture of biopharmaceuticals and therapeutics, announces an ... the 2016 BioProcess International Awards – Recognizing Excellence in the People, Organizations ...
(Date:2/11/2016)... 2016   BioInformant announces the February 2016 ... Products, Opportunities, Tools, and Technologies – Market Size, Segments, ... The first and only ... industry, BioInformant has more than a decade of historical ... by stem cell type. This powerful 175 page global ...
(Date:2/11/2016)... (PRWEB) , ... February 11, 2016 , ... ... of its new stem cell treatment clinic in Quito, Ecuador. The new facility ... and trauma applications to patients from around the world. , The new ...
Breaking Biology Technology: