humanin and Neoplasms

Humanin (HN) is a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA. HN exhibits protective effects in several cell types, including leukocytes, germ cells, neurons, tissues against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein. HN is an essential cytoprotective peptide in the human body that regulates mitochondrial functions under stress conditions. The present review aims to evaluate HN peptide's antiapoptotic activities as a potential therapeutic target in the treatment of cancer, diabetes mellitus, male infertility, bone-related diseases, cardiac diseases, and brain diseases. Based on in vitro and in vivo studies, HN significantly suppressed the apoptosis during the treatment of bone osteoporosis, cardiovascular diseases, diabetes mellitus, and neurodegenerative diseases. According to accumulated data, it is concluded that HN exerts the proapoptotic activity of TNF-α in cancer, which makes HN as a novel therapeutic agent in the treatment of cancer and suggested that along with HN, the development of another mitochondrial-derived peptide could be a viable therapeutic option against different oxidative stress and apoptosis-related diseases.

Topics: Amino Acid Sequence; Animals; Apoptosis; Apoptosis Regulatory Proteins; Cytoprotection; Diabetes Mellitus; Humans; Intracellular Signaling Peptides and Proteins; Mitochondria; Neoplasms; Neurodegenerative Diseases

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.

Topics: Animals; Cardiovascular Diseases; Disease Models, Animal; Genetic Therapy; Humans; Intracellular Signaling Peptides and Proteins; Mitochondria; Molecular Targeted Therapy; Neoplasms; Neurodegenerative Diseases

Topics: Biopsy; Electric Impedance; Humans; Intracellular Signaling Peptides and Proteins; Needles; Neoplasms

The basis of a bacterial pathogenic process consists in the change of a certain host structure to a completely different one. This is accomplished by binding of a bacterial protein product to the host structure. Streptococcal NAD+-nucleosidase was explored as to its binding to the host receptor represented by beef heart extract. The bacterial product was found to bind to the host structure until the available host structure was fully saturated. The similarity of the above flows of macromolecules with some models of morphogenesis indicates the existence of diseases associated with the flow of a protein to the undesirable site in the organism. In such a case therapy with low-molar-mass substances is wrong in principle.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Bacterial Proteins; Biomarkers, Tumor; Humans; Intracellular Signaling Peptides and Proteins; Models, Biological; Myocardium; NAD+ Nucleosidase; Neoplasms; Peptides; Protein Binding; Streptococcus pyogenes