Journal
EXPERT OPINION ON THERAPEUTIC TARGETS
Volume 18, Issue 2, Pages 185-208Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.2014.856417
Keywords
autoimmunity; cancer; carboranylphenoxyacetanilide; chaperonopathies; chaperonotherapy; chemical compounds; Cpn60; electrophilic compounds; epolactaene; functional domain; GroEL; Hsp60; inflammation; mizoribine; structural domain
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Funding
- IEMEST
- University of Palermo
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Introduction: Hsp60 (Cpn60) assembles into a tetradecamer that interacts with the co-chaperonin Hsp10 (Cpn10) to assist client polypeptides to fold, but it also has other roles, including participation in pathogenic mechanisms. Area covered: Hsp60 chaperonopathies are pathological conditions, inherited or acquired, in which the chaperone plays a determinant etiologic-pathogenic role. These diseases justify selection of Hsp60 as a target for developing agents that interfere with its pathogenic effects. We provide information on how to proceed. Expert opinion: The information available encourages the development of ways to improve Hsp60 activity (positive chaperonotherapy) when deficient or to block it (negative chaperonotherapy) when pathogenic. Many questions are still unanswered and obstacles are obvious. More information is needed to establish when and why autologous Hsp60 becomes a pathogenic autoantigen, or induces cytokine formation and inflammation, or favors carcinogenesis. Clarification of these points will take considerable time. However, analysis of the Hsp60 molecule and a search for active compounds aimed at structural sites that will affect its functioning should continue without interruption. No doubt that some of these compounds will offer therapeutic hopes and will also be instrumental for dissecting structure--function relationships at the biochemical and biological (using animal models and cultured cells) levels.
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