Pharmacoperones for misfolded gonadotropin receptors

The gonadotropin receptors (luteinising hormone receptor; LHR and follicle-stimulating hormone receptor; FSHR) are G protein-coupled receptors (GPCRs) that play an important role in the endocrine control of reproduction. Thus genetic mutations that cause impaired function of these receptors have been implicated in a number of reproductive disorders. Disease-causing genetic mutations in GPCRs frequently result in intracellular retention and degradation of the nascent protein through misfolding and subsequent recognition by cellular quality control machinery. The discovery and development of novel compounds termed pharmacological chaperones (pharmacoperones) that can stabilise misfolded receptors and restore trafficking and plasma membrane expression are therefore of great interest clinically, and promising in vitro data describing the pharmacoperone rescue of a number of intracellularly retained mutant GPCRs has provided a platform for taking these compounds into in vivo trials. Thienopyrimidine small molecule allosteric gonadotropin receptor agonists (Org 42599 and Org 41841) have been demonstrated to have pharmacoperone activity. These compounds can rescue cell surface expression and in many cases, hormone responsiveness, of a range of retained mutant gonadotropin receptors. Should gonadotropin receptor selectivity of these compounds be improved, they could offer therapeutic benefit to subsets of patients suffering from reproductive disorders attributed to defective gonadotropin receptor trafficking.https://www.springer.com/series/1642018-12-01hj2018Immunolog

Corporate social responsibility reporting:a content analysis in family and non-family firms

Family firms are ubiquitous and play a crucial role across all world economies, but how they differ in the disclosure of social and environmental actions from non-family firms has been largely overlooked in the literature. Advancing the discourse on corporate social responsibility reporting, we examine how family influence on a business organization affects CSR reporting. The arguments developed here draw on institutional theory, using a rich body of empirical evidence gathered through a content analysis of the CSR reports of 98 large and medium-sized Italian firms. The grounded theory analysis informs and contextualizes several differences in the type and content of corporate social responsibility reports of family and non-family firms. Our findings show that in comparison to non-family firms, family firms disseminate a greater variety of CSR reports, are less compliant with CSR standards and place emphasis on different CSR topics. We thus contribute to family business and corporate social responsibility reporting literatures in several ways, offering implications for practice and outlining promising avenues for future research