HOME >> BIOLOGY >> NEWS
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 (PA28) 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 Huntingtons 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 demon
'"/>

Contact: Professor Ole Isacson
isacson@hms.harvard.edu
617-855-3243
Public Library of Science
27-Feb-2007


Page: 1 2

Related biology news :

1. Cancer drug enhances long-term memory
2. Dartmouth researchers identify a gene that enhances muscle performance
3. Getting ahead of cancer: SPECT/Spiral CT technology enhances bone scanning, earlier diagnosis
4. NYU algorithm enhances ability to detect cancer genes
5. Delft mathematician enhances protectiveness of military uniform
6. Elevated temperature enhances success of viral cancer therapy
7. Pulsating ultrasound enhances gene therapy for tumors
8. Moderate alcohol consumption enhances the formation of new nerve cells
9. New use for a cell toxin found to inhibit survival proteins in cancer cells
10. Glimmer of hope for Tahitian tree snails survival
11. Nexavar significantly extends overall survival by 44 percent in liver cancer patients

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:8/5/2020)... ... , ... Regenative Labs has received approval from the Centers for Medicare & ... first Wharton’s jelly allografts to be assigned a Q code and be approved for ... Wharton’s jelly allograft product to be recognized as a 361 HCT/P by CMS regulated ...
(Date:7/18/2020)... ... July 16, 2020 , ... A study has been published ... Neoasis™ active noise control device to attenuate typical noises in a simulated neonatal ... the alarm sounds from patient monitors, ventilators and other bedside devices that would ...
(Date:7/2/2020)... ... July 01, 2020 , ... AltruBio Inc. http://www.altrubio.com ... a biologic for the treatment of steroid-refractory acute graft-versus-host disease (SR-aGVHD), at European ... J Martin of the Fred Hutchinson Cancer Research Center, this single-arm, open-label Phase ...
Breaking Biology News(10 mins):
(Date:8/12/2020)... FARMS, Mich. (PRWEB) , ... August 12, 2020 ... ... Consulting Group, Inc. (EMMA International), a global leader in FDA compliance consulting ... of the nation’s fastest-growing private companies. The list represents a unique look at ...
(Date:8/3/2020)... (PRWEB) , ... August 03, 2020 , ... ... collection, today announced Jim Corrigan, President and CEO has been named one of ... broad cross-section of industry sectors, PharmaVoice 100 honorees are selected based on how ...
(Date:7/31/2020)... ... July 29, 2020 , ... R3 Stem Cell International is ... $3950. With 50 million stem cells total, patients may choose which extremities they would ... for arthritic joints (BMC Musculoskelet Disord. 2016). At R3 International, umbilical cord tissue is ...
(Date:7/31/2020)... ... July 29, 2020 , ... ... transmitter systems that can be configured to drive Klystrons, TWTs, IOTs, and magnetrons. ... drive one or two switches in a push-pull configuration; yielding fast fall time ...
Breaking Biology Technology:
Cached News: