New Therapeutic Strategies for Cancer and Neurodegeneration Emerging from Yeast Cell-based Systems

被引:22
作者
Pereira, Clara [1 ]
Leao, Mariana [1 ]
Soares, Joana [1 ]
Bessa, Claudia [1 ]
Saraiva, Lucilia [1 ]
机构
[1] Univ Porto, Fac Pharm, Microbiol Lab, REQUIMTE,Dept Biol Sci, P-4050313 Oporto, Portugal
关键词
Yeast; cancer; neurodegeneration; drug discovery; therapeutic targets; target-based screening; genome-wide screening; PROTEIN-KINASE-C; MUTANT HUNTINGTIN FRAGMENT; ALPHA-SYNUCLEIN TOXICITY; GROWTH SELECTION SYSTEM; SACCHAROMYCES-CEREVISIAE; IN-VIVO; GENE-EXPRESSION; SMALL MOLECULES; DIFFERENTIAL ACTIVATION; TRANSCRIPTION FACTOR;
D O I
10.2174/138161212802430422
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
Despite great advances in understanding the molecular etiology of cancer and neurodegeneration, therapeutic strategies against these diseases are still largely lacking. Hence, acceleration of the discovery of new therapeutic agents against these pathologies is of enormous interest. This review is focused on the role of multi-faceted and expanding yeast cell-based systems in the search for new drugs and therapeutic targets in cancer and neurodegeneration. Though the obvious limitations of using a microorganism to address human diseases, when used in the early phase and with complementary mammalian systems, it can have a tremendous impact in the discovery of new therapeutic opportunities. In this review, many evidence are provided demonstrating the valuable contribution of yeast in this area. Additionally, several yeast target-based drug screening approaches based on a readily screenable phenotype on genomic technologies increasingly oriented towards genetic and chemical high-throughput analysis are addressed. Altogether, with this review, we intend not only to recognize previous successes and ongoing work in this area, but also to point out new opportunities that may be of interest for yeast as a model organism and as a powerful system in the discovery of new lead compounds that have the potential to become novel drugs in cancer and neurodegeneration.
引用
收藏
页码:4223 / 4235
页数:13
相关论文
共 123 条
[1]
p53 Transactivation and the Impact of Mutations, Cofactors and Small Molecules Using a Simplified Yeast-Based Screening System [J].
Andreotti, Virginia ;
Ciribilli, Yari ;
Monti, Paola ;
Bisio, Alessandra ;
Lion, Mattia ;
Jordan, Jennifer ;
Fronza, Gilberto ;
Menichini, Paola ;
Resnick, Michael A. ;
Inga, Alberto .
PLOS ONE, 2011, 6 (06)
[2]
TDP-43 toxicity in yeast [J].
Armakola, Maria ;
Hart, Michael P. ;
Gitler, Aaron D. .
METHODS, 2011, 53 (03) :238-245
[3]
Pharmacological Activation of p53 in Cancer Cells [J].
Athar, Mohammad ;
Elmets, Craig A. ;
Kopelovich, Levy .
CURRENT PHARMACEUTICAL DESIGN, 2011, 17 (06) :631-639
[4]
Isolation of drugs active against mammalian prions using a yeast-based screening assay [J].
Bach, S ;
Talarek, N ;
Andrieu, T ;
Vierfond, JM ;
Mettey, Y ;
Galons, H ;
Dormont, D ;
Meijer, L ;
Cullin, C ;
Blondel, M .
NATURE BIOTECHNOLOGY, 2003, 21 (09) :1075-1081
[5]
Modulation of Aβ42 low-n oligomerization using a novel yeast reporter system [J].
Bagriantsev, Sviatoslav ;
Liebman, Susan .
BMC BIOLOGY, 2006, 4 (1)
[6]
Barberis A, 2005, DRUG DISCOV TODAY TE, V2, P5
[7]
A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors [J].
Becker, F ;
Murthi, K ;
Smith, C ;
Come, J ;
Costa-Roldán, N ;
Kaufmann, C ;
Hanke, U ;
Degenhart, C ;
Baumann, S ;
Wallner, W ;
Huber, A ;
Dedier, S ;
Dill, S ;
Kinsman, D ;
Hediger, M ;
Bockovich, N ;
Meier-Ewert, S ;
Kluge, AF ;
Kley', N .
CHEMISTRY & BIOLOGY, 2004, 11 (02) :211-223
[8]
Identification of a small molecule inhibitor of Sir2p [J].
Bedalov, A ;
Gatbonton, T ;
Irvine, WP ;
Gottschling, DE ;
Simon, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (26) :15113-15118
[9]
Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington's and Parkinson's diseases [J].
Bodner, RA ;
Outeiro, TF ;
Altmann, S ;
Maxwell, MM ;
Cho, SH ;
Hyman, BT ;
McLean, PJ ;
Young, AB ;
Housman, DE ;
Kazantsev, AG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (11) :4246-4251
[10]
HMGB1 inhibits cell death in yeast and mammalian cells and is abundantly expressed in human breast carcinoma [J].
Brezniceanu, ML ;
Völp, K ;
Bösse, S ;
Solbach, C ;
Lichter, P ;
Joos, S ;
Zörnig, M .
FASEB JOURNAL, 2003, 17 (08) :1295-+