Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases

ASAD, ANTONELA SOFIA; MORENO AYALA, MARIELA ALEJANDRA; CANDOLFI, MARIANELA; ZUCCATO, CAMILA FLORENCIA; GOTTARDO, MARÍA FLORENCIA; SEILICOVICH, ADRIANA; NICOLA CANDIA, ALEJANDRO JAVIER; THEAS, MARÍA SUSANA

EXPERT OPINION ON THERAPEUTIC TARGETS

INFORMA HEALTHCARE

Año: 2019 vol. 23 p. 117 - 126

1472-8222

Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome and 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 different chronic diseases. Areas covered: Here we describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenative diseases, cardiovascular disorders, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as biomarker for these diseases. Expert Opinion: HN analogs and peptide mimetics have been developed over the last decade, showing promising results in preclinical models of degenerative diseases. In spite of the limitations in their biodistribution have been overcome by the recent development of a peptide mimetic that crosses the blood-brain barrier. 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 needs to be addressed before the translation of these therapeutic approaches.