Nematode Hsp90: highly conserved but functionally diverse

Gillan, Victoria; Devaney, Eileen

doi:10.1017/s0031182014000304

Cited by 13 publications

(11 citation statements)

References 103 publications

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“…HSP90 is ubiquitously expressed and is one of the most abundant intracellular proteins in mammalian cells and folds a wide range of proteins involved in signal transduction, assembly and trafficking [16]. With more than 200 known client proteins, it has been recognized as a potential target for a number of diseases associated with aberrant protein signaling including cancer, neurodegeneration and infectious diseases [17-20]. The high abundance of HSP90, its presence in normal cells and its recognized housekeeping function would seem to suggest that it is a poor target and that efforts to develop drugs against it would be futile.…”

Section: Hsp90 As a Target In Diseasementioning

confidence: 99%

Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease

Shrestha¹,

Bolaender²,

Patel³

et al. 2016

CTMC

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Heat shock proteins (HSPs) present as a double edged sword. While they play an important role in maintaining protein homeostasis in a normal cell, cancer cells have evolved to co-opt HSP function to promote their own survival. As a result, HSPs such as HSP90 have attracted a great deal of interest as a potential anticancer target. These efforts have resulted in over 20 distinct compounds entering clinical evaluation for the treatment of cancer. However, despite the potent anticancer activity demonstrated in preclinical models, to date no HSP90 inhibitor has obtained regulatory approval. In this review we discuss the unique challenges faced in targeting HSPs that have likely contributed to their lack of progress in the clinic and suggest ways to overcome these so that the enormous potential of these compounds to benefit patients can finally be realized. We also provide a guideline for the future development of HSP-targeted agents based on the many lessons learned during the last two decades in developing HSP90 inhibitors.

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Section: Hsp90 As a Target In Diseasementioning

confidence: 99%

Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease

Shrestha¹,

Bolaender²,

Patel³

et al. 2016

CTMC

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“…In contrast, parasites in which the free-living stage is enclosed within a protective egg, or obligate parasites such as filarial nematodes, which never encounter the environment, are under no such pressure [49]. We next attempted to determine whether there was evidence of adaptive evolution in nematode hsp90 sequences in support of this hypothesis.…”

Section: Hsp90 Differs In Free-living and Parasitic Nematodesmentioning

confidence: 99%

Hsp90 Inhibitors in Parasitic Nematodes: Prospects and Challenges

Devaney

Gillan²

2016

CTMC

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Hsp90 inhibitors are well characterized in relation to their effects in a variety of tumors, with several inhibitors in various phases of clinical development. In recent years, the same inhibitor classes have been tested for efficacy in other systems, such as Alzheimer's disease and a variety of infectious disease models, including fungal and parasitic targets. In this article we discuss the repurposing of Hsp90 inhibitors for parasitic disease with a focus on parasitic nematode infections. We summarize the data that indicates that Hsp90 is functionally diverse in different nematode species and we discuss the challenges and prospects for developing these inhibitors as next generation chemotherapeutic tools.

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“…The female-enriched set also contained key ribosomal proteins, heat shock proteins and chaperonins (Fig. 5), likely to be involved in reproductive processes and possibly host-pathogen-interactions (Gillan and Devaney, 2014). Interestingly, a gene (OESDEN_15934) encoding an endonuclease (CRN-1, the C. elegans homolog of FEN-1) likely to be intimately involved in switching the state of cells from DNA replication/repair to DNA degradation during apoptosis (Nisbet et al, 2008; Parrish et al, 2003) was highly transcribed in females (Fig.…”

Section: Gender-enriched Transcriptionmentioning

confidence: 99%

Cracking the nodule worm code advances knowledge of parasite biology and biotechnology to tackle major diseases of livestock

Tyagi

Joachim

Ruttkowski

et al. 2015

Biotechnology Advances

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Many infectious diseases caused by eukaryotic pathogens have a devastating, long-term impact on animal health and welfare. Hundreds of millions of animals are affected by parasitic nematodes of the order Stronglida. Unlocking the molecular biology of representatives of this order, and understanding nematode-host interactions, drug resistance and disease using advanced technologies could lead to entirely new ways of controlling the diseases that they cause. Oesphagostomum dentatum (nodule worm; superfamily Strongyloidea) is an economically important strongylid nematode of swine worldwide. The present article reports recent advances made in biology and animal biotechnology through the draft genome and developmental transcriptome of O. dentatum, in order to support biological research of this and related parasitic nematodes as well as the search for new and improved interventions. This first genome of any member of the Strongyloidea is 443 Mb in size and predicted to encode 25,291 protein-coding genes. Here, we review the dynamics of transcription throughout the life cycle of O. dentatum, describe double-stranded RNA interference (RNAi) machinery and infer molecules involved in development and reproduction, and in inducing or modulating immune responses or disease. The secretome predicted for O. dentatum is particularly rich in peptidases linked to interactions with host tissues and/or feeding activity, and a diverse array of molecules likely involved in immune responses. This research progress provides an important resource for future comparative genomic and molecular biological investigations as well as for biotechnological research toward new anthelmintics, vaccines and diagnostic tests.

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Nematode Hsp90: highly conserved but functionally diverse

Cited by 13 publications

References 103 publications

Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease

Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease

Hsp90 Inhibitors in Parasitic Nematodes: Prospects and Challenges

Cracking the nodule worm code advances knowledge of parasite biology and biotechnology to tackle major diseases of livestock

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