Proteasome Inhibitors

Publication Title: 
Aging Cell

Proteasome-dependent degradation has been extensively investigated and has been shown to play a vital role in the maintenance of cellular homeostasis. Proteasome activity and expression are reduced during aging and replicative senescence. Its activation has been shown to confer lifespan extension in human diploid fibroblasts (HDFs), whereas partial proteasome inhibition triggers an irreversible premature senescent state in young HDFs.

Author(s): 
Chondrogianni, Niki
Trougakos, Ioannis P.
Kletsas, Dimitris
Chen, Qin M.
Gonos, Efstathios S.
Publication Title: 
Nature

Embryonic stem cells can replicate continuously in the absence of senescence and, therefore, are immortal in culture. Although genome stability is essential for the survival of stem cells, proteome stability may have an equally important role in stem-cell identity and function. Furthermore, with the asymmetric divisions invoked by stem cells, the passage of damaged proteins to daughter cells could potentially destroy the resulting lineage of cells. Therefore, a firm understanding of how stem cells maintain their proteome is of central importance.

Author(s): 
Vilchez, David
Boyer, Leah
Morantte, Ianessa
Lutz, Margaret
Merkwirth, Carsten
Joyce, Derek
Spencer, Brian
Page, Lesley
Masliah, Eliezer
Berggren, W. Travis
Gage, Fred H.
Dillin, Andrew
Publication Title: 
Malaria Journal

BACKGROUND: The emergence and spread of Plasmodium falciparum resistance to almost all available antimalarial drugs necessitates the search for new chemotherapeutic compounds. The ubiquitin/proteasome system plays a major role in overall protein turnover, especially in fast dividing eukaryotic cells including plasmodia. Previous studies show that the 20S proteasome is expressed and catalytically active in plasmodia and treatment with proteasome inhibitors arrests parasite growth.

Author(s): 
Kreidenweiss, Andrea
Kremsner, Peter G.
Mordmüller, Benjamin
Publication Title: 
Antimicrobial Agents and Chemotherapy

Despite declining numbers of cases and deaths, malaria remains a major public health problem in many parts of the world. Today, case management relies heavily on a single class of antimalarial compounds: artemisinins. Hence, development of resistance against artemisinins may destroy current malaria control strategies. Beyond malaria control are elimination and eradication programs that will require drugs with good activity against acute infection but also with preventive and transmission-blocking properties.

Author(s): 
Tschan, Serena
Brouwer, Arwin J.
Werkhoven, Paul R.
Jonker, Anika M.
Wagner, Lena
Knittel, Sarah
Aminake, Makoah Nigel
Pradel, Gabriele
Joanny, Fanny
Liskamp, Rob M. J.
Mordmüller, Benjamin
Publication Title: 
PloS One

The medicinal plant Withania somnifera has been used for over centuries in Indian Ayurvedic Medicine to treat a wide spectrum of disorders. Withaferin A (WA), a bioactive compound that is isolated from this plant, has anti-inflammatory, immuno-modulatory, anti-angiogenic, and anti-cancer properties. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of WA and the molecular mechanisms involved.

Author(s): 
Yang, Huanjie
Wang, Ying
Cheryan, Vino T.
Wu, Wenjuan
Cui, Cindy Qiuzhi
Polin, Lisa A.
Pass, Harvey I.
Dou, Q. Ping
Rishi, Arun K.
Wali, Anil
Publication Title: 
BMC complementary and alternative medicine

BACKGROUND: Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine.

Author(s): 
Noolu, Bindu
Ajumeera, Rajanna
Chauhan, Anitha
Nagalla, Balakrishna
Manchala, Raghunath
Ismail, Ayesha
Publication Title: 
Cell Death & Disease

Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation.

Author(s): 
Khedgikar, V.
Kushwaha, P.
Gautam, J.
Verma, A.
Changkija, B.
Kumar, A.
Sharma, S.
Nagar, G. K.
Singh, D.
Trivedi, P. K.
Sangwan, N. S.
Mishra, P. R.
Trivedi, R.
Publication Title: 
PloS One

The medicinal plant Withania somnifera has been used for over centuries in Indian Ayurvedic Medicine to treat a wide spectrum of disorders. Withaferin A (WA), a bioactive compound that is isolated from this plant, has anti-inflammatory, immuno-modulatory, anti-angiogenic, and anti-cancer properties. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of WA and the molecular mechanisms involved.

Author(s): 
Yang, Huanjie
Wang, Ying
Cheryan, Vino T.
Wu, Wenjuan
Cui, Cindy Qiuzhi
Polin, Lisa A.
Pass, Harvey I.
Dou, Q. Ping
Rishi, Arun K.
Wali, Anil
Publication Title: 
BMC complementary and alternative medicine

BACKGROUND: Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine.

Author(s): 
Noolu, Bindu
Ajumeera, Rajanna
Chauhan, Anitha
Nagalla, Balakrishna
Manchala, Raghunath
Ismail, Ayesha
Publication Title: 
Cell Death & Disease

Withania somnifera or Ashwagandha is a medicinal herb of Ayurveda. Though the extract and purified molecules, withanolides, from this plant have been shown to have different pharmacological activities, their effect on bone formation has not been studied. Here, we show that one of the withanolide, withaferin A (WFA) acts as a proteasomal inhibitor (PI) and binds to specific catalytic β subunit of the 20S proteasome. It exerts positive effect on osteoblast by increasing osteoblast proliferation and differentiation.

Author(s): 
Khedgikar, V.
Kushwaha, P.
Gautam, J.
Verma, A.
Changkija, B.
Kumar, A.
Sharma, S.
Nagar, G. K.
Singh, D.
Trivedi, P. K.
Sangwan, N. S.
Mishra, P. R.
Trivedi, R.

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