Peptide and Protein Chemistry
New insights and developments to open translational opportunities.
Apoptosis (programmed cell death) is executed by strongly regulated pathways, and serve to remove infected, damaged or ectopic cells. The intrinsic pathway of apoptosis is initiated by many stresses inducing mitochondrial outer membrane permeabilisation (MOMP) mediated by proteins of the Bcl-2 family. Cytochrome c is then released into the cytosol and induces the formation of the apoptosome complex. Apoptosis dysregulation is at the root of a variety of diseases. While resistance has been linked to cancer and autoimmune diseases, excessive apoptosis is connected to neurodegeneration and ischemia-reperfusion damage. Apoptosis can be modulated through links with other cell signaling pathways. Then, apoptosis proteins can participate and cross-talk to non-apoptotic processes, such as cell differentiation and proliferation, mitochondrial morphogenesis, autophagy and inflammation.
Apoptosis susceptibility is co-determined by a multifactorial interplay but the molecular mechanisms and controls remain poorly understood. We aim to investigate how apoptosis is integrated, interrelated and modulated. To this end, we develop chemical tools to gain quantitative molecular information to understand physiological (light) and pathophysiological (dark) modes of apoptosis modulation. We believe that our approach will facilitate the knowledge-driven identification and development of targeted pharmacological interventions that modulate cell death susceptibility.
Identification and validation of uterine stimulant methylergometrine as a potential inhibitor of caspase-1 activation.
García-Laínez G, Sancho M, García-Bayarri V, Orzáez M
Apoptosis : an international journal on programmed cell death , 2017 Oct, vol. 22, pag. 1310-1318
Targeting inflammasome by the inhibition of caspase-1 activity using capped mesoporous silica nanoparticles.
García-Fernández A, García-Laínez G, Ferrándiz ML, Aznar E, Sancenón F, Alcaraz MJ, Murguía JR, Marcos MD, Martínez-Máñez R, Costero AM, Orzáez M
Journal of controlled release : official journal of the Controlled Release Society , 2017 Feb 28, vol. 248, pag. 60-70
Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes.
Andreu-Fernández V, Sancho M, Genovés A, Lucendo E, Todt F, Lauterwasser J, Funk K, Jahreis G, Pérez-Payá E, Mingarro I, Edlich F, Orzáez M
Proceedings of the National Academy of Sciences of the United States of America , 2017 Jan 10, vol. 114, pag. 310-315
Caspase 3 Targeted Cargo Delivery in Apoptotic Cells Using Capped Mesoporous Silica Nanoparticles.
de la Torre C, Mondragón L, Coll C, García-Fernández A, Sancenón F, Martínez-Máñez R, Amorós P, Pérez-Payá E, Orzáez M
Chemistry (Weinheim an der Bergstrasse, Germany) , 2015 Oct 26, vol. 21, pag. 15506-10
Apaf-1 inhibitors protect from unwanted cell death in in vivo models of kidney ischemia and chemotherapy induced ototoxicity.
Orzáez M, Sancho M, Marchán S, Mondragón L, Montava R, Valero JG, Landeta O, Basañez G, Carbajo RJ, Pineda-Lucena A, Bujons J, Moure A, Messeguer A, Lagunas C, Herrero C, Pérez-Payá E
PloS one , 2014 Oct 20, vol. 9, pag. e110979