title: Autophagy as a target for therapeutic uses of multifunctional peptides.
abstract: The emergence of complex diseases is promoting a change from one-target to multitarget drugs and peptides are ideal molecules to fulfill this polypharmacologic role. Here we review current status in the design of polypharmacological peptides aimed to treat complex diseases, focusing on tuberculosis. In this sense, combining multiple activities in single molecules is a two-sided sword, as both positive and negative side effects might arise. These polypharmacologic compounds may be directed to regulate autophagy, a catabolic process that enables cells to eliminate intracellular microbes (xenophagy), such as Mycobacterium tuberculosis (MBT). Here we review some strategies to control MBT infection and propose that a peptide combining both antimicrobial and pro-autophagic activities would have a greater potential to limit MBT infection. This endeavor may complement the knowledge gained in understanding the mechanism of action of antibiotics and may lead to the design of better polypharmacological peptides to treat complex diseases such as tuberculosis.
authors.affiliation: Department of Neurodevelopment and Physiology, Instituto De Fisiología Celular, UNAM, México, D.F, México.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Muciño
authors.affiliation: Department of Neurodevelopment and Physiology, Instituto De Fisiología Celular, UNAM, México, D.F, México.
authors.forename: Susana
authors.initials: S
authors.lastname: Castro-Obregón
authors.affiliation: Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition "Salvador Zubirán,", Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernandez-Pando
authors.affiliation: Department of Biochemistry and Structural Biology, Instituto De Fisiología Celular, UNAM, México, D.F, México.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Del Rio
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000276:immunology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology; D058990:Molecular Targeted Therapy; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D010586:Phagocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C518959:ATG16L1 protein, human; D023181:Antimicrobial Cationic Peptides; D000995:Antitubercular Agents; D000071183:Autophagy-Related Proteins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; C513539:IRGM protein, human
keywords: antimicrobial peptides; autophagy; polypharmacology; tuberculosis