RESUMO
Resumen La humanina es un péptido derivado de la mitocondria con efectos protectores robustos contra una gran variedad de estímulos citotóxicos en diversos tipos celulares. Esto la convierte en un blanco terapéutico interesante para muchas enfermedades, como el cáncer y enfermedades neurodegenerativas, entre otras. Además, este péptido podría utilizarse como un biomarcador en estas enfermedades. Durante la última década, han sido desarrollados análogos y péptido-miméticos de la humanina que muestran resultados prometedores en modelos preclínicos. A su vez, también se está explorando el potencial terapéutico de vectores de terapia génica que puedan sobreexpresar o silenciar la humanina endógena. Varios puntos importantes a considerar antes de trasladar estas estrategias terapéuticas a la clínica son su posible papel en la progresión del cáncer y la eventual generación de quimiorresistencia. Todos estos temas serán abordados en este artículo de revisión.
Abstract Humanin is a mitochondrial-derived peptide which shows robust protective effects against large series of cytotoxic stimuli in many cell types. This makes it an interesting therapeutic target for many diseases, including cancer and neurodegenerative diseases, among others. Furthermore, this peptide could be used as a biomarker for such diseases. Over the last decade, humanin analogs and peptide mimetics have been developed, which exert highly promising results in preclinical models. Besides, the therapeutic potential of gene therapy vectors that overexpress or silence endogenous humanin is under evaluation. Nonetheless, its possible role in cancer progression and chemoresistance are critical issues to be addressed before translating these therapeutic approaches to the clinic. All these matters will be covered in this review.
Assuntos
Doenças Neurodegenerativas , Volição , Doença , NeoplasiasRESUMO
INTRODUCTION: Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome. They signal within the cell or are released to act as autocrine/paracrine/endocrine cytoprotective factors playing a key role in the cellular stress response. The first reported and better characterized MDP is humanin (HN), which exerts robust protective effects against a myriad of cytotoxic stimuli in many cell types. These effects have led to the evaluation of HN and its analogs as therapeutic targets for several chronic diseases. Areas covered: We describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenerative and cardiovascular diseases, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as a biomarker for these diseases. Expert opinion: HN analogs and peptide mimetics have been developed over the last decade and show promising results in preclinical models of degenerative diseases. Local administration of gene therapy vectors that overexpress or silence endogenous HN could also hold therapeutic potential. Controversy on the role of HN in cancer progression and chemoresistance should be addressed before the translation of these therapeutic approaches.
