Projects 13 and 14
President of Fundación Teófilo Hernando (FTH) and Emeritus Professor of Pharmacology at the Universidad Autónoma de Madrid, Spain.
- Neurochemistry and pharmacology of neurotransmission
- Pharmacological neuroprotection
The studies of the pharmacological and neurochemical regulation of ion channels and calcium signaling have been the focus of my laboratory since 1975. I have projected these studies towards the understanding of the basic principles governing the exocytotic release of catecholamine, neuronal survival, and neuronal death. More recently, my laboratory is making efforts to translate this accumulated knowledge to the understanding of altered neurotransmitter release and cell vulnerability in neurodegenerative processes, particularly Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD).
Ultimately, the overall effort addresses the search of a neuroprotective medicine capable of delaying AD and/or ALS progression and improve the quality of life of patients suffering these terrible diseases. I recently created the spinoff DNS Neuroscience to ease the transfer of my laboratory knowledge to society.
In the context of PurinesDX the multidisciplinary team that is developing Beneficiary Group 9/FTH objectives, under PI Antonio G. García, is composed of medicinal chemists (Cristóbal de los Ríos), electrophysiologists (Luis Gandía, Antonio Miguel G. de Diego), neuropharmacologists (Fernando Padín) and molecular biologists (María F. Cano-Abad). Some publications linked to the project are as follows:
- LÓPEZ-GIL A, NANCLARES C, MÉNDEZ-LÓPEZ I, MARTÍNEZ-RAMÍREZ C, DE LOS RIOS C, PADÍN-NOGUEIRA JF, MONTERO M, GANDÍA L, GARCÍA A.G. The quantal catecholamine release from mouse chromaffin cells challenged with repeated ACh pulses is regulated by the mitochondrial Na+ /Ca2+ exchanger. J Physiol. 2017;595:2129-2146.
- 2. PUNZÓN E, GARCÍA-ALVARADO F, MAROTO M, FERNÁNDEZ-MENDÍVIL C, MICHALSKA P, GARCÍA-ÁLVAREZ I, ARRANZ-TAGARRO JA, BUENDIA I, LÓPEZ MG, LEÓN R, GANDÍA L, FERNÁNDEZ-MAYORALAS A, GARCÍA A.G. Novel sulfoglycolipid IG20 causes neuroprotection by activating the phase II antioxidant response in rat hippocampal slices. Neuropharmacology. 2016;116:110-121.
- LAJARÍN-CUESTA R, PEREZ-DE-NANCLARES C, ARRANZ-TAGARRO JA, BRITO-ARAUJO M; GONZALEZ-LAFUENTE L, ARRIBAS RL, GANDÍA L, DE LOS RIOS C. Gramine derivatives targeting Ca2+ channels and Ser/Thr phosphatases: a new dual approach for the treatment of neurodegenerative diseases. J. Med. Chem. 2016; 59: 6265-6280.
- MARTÍNEZ-SANZ FJ, LAJARÍN-CUESTA R, GONZÁLEZ-LAFUENTE L, MORENO-ORTEGA AJ, PUNZÓN E, CANO-ABAD MF, DE LOS RIOS C. Neuroprotective profile of pyridothiazepines with blocking activity of the mitochondrial Na+/Ca2+ exchanger. Eur. J. Med. Chem. 2016, 109: 114-123.
- CALVO-GALLARDO, E., DE PASCUAL, R., FERNÁNDEZ-MORALES, J.C., ARRANZ-TAGARRO, J.A., MAROTO, M., NANCLARES, C., GANDIA, L., DE DIEGO, A.M.G., PADÍN, J.F. and GARCÍA, A.G.Depressed excitability and ion currents linked to slow exocytotic fusion pore in chromaffin cells of the SOD1G93A mouse model of amyotrophic lateral sclerosis. Am. J. Physiol. 308: C1-C19, 2015.
- FERNÁNDEZ-BACHILLER, M.I., PÉREZ, C., GONZÁLEZ-MUÑOZ, G.C., CONDE, S. LÓPEZ, M.G., VILLARROYA, M., GARCIA, A.G.and RODRÍGUEZ-FRANCO, I. Novel tacrine–8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer’s disease, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties. J. Med. Chem. 53: 4927-4937, 2010
- GARCIA, A.G., GARCIA-DE-DIEGO, A.M., GANDIA, L., BORGES, R. and GARCIA-SANCHO, J.: Calcium signalling and exocytosis in adrenal chromaffin cells. Physiol. Rev. 86: 1093-1131, 2006.
- ARIAS, E., ALES, E., GABILAN, N.H., CANO-ABAD, M.F., VILLARROYA, M., GARCIA, A.G. and LOPEZ, M.G.: Galantamine prevents apoptosis induced by b-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors. Neuropharmacology46: 103-114, 2004.
- MONTERO, M., ALONSO, M.T., CARNICERO, E., CUCHILLO, E., ALBILLOS, A., GARCIA, A.G., GARCIA-SANCHO, J. and ALVAREZ, J.: Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+transients that modulate secretion. Nature Cell Biol. 2: 57-61, 2000.
- GANDIA, L., GARCIA, A.G.and MORAD, M.: ATP modulation of calcium channels in chromaffin cells. J. Physiol. 470: 55-72, 1993.
- GARCIA, A.G., SALA, F., REIG, J.A., VINIEGRA, S., FRIAS, J., FONTERIZ, R. and GANDIA, L.: Dihydropyridine BAY-K-8644 activates chromaffin cell calcium channels. Nature309: 69-71, 1984.
- GARCIA, A.G.and KIRPEKAR, S.M.: Release of noradrenaline from slices of cat spleen by pretreatment with calcium, strontium and barium. J. Physiol. 235: 683-713, 1973.
About Teófilo Hernando Foundation
“Fundación Teófilo Hernando” (FTH, Teófilo Hernando’s Foundation) is a private non-profit organization. It was created in 1993 under the name of professor Teófilo Hernando, who pioneered the introduction and development of pharmacology in Spanish Universities, at the beginning of the XX Century. FTH is tightly linked to “Instituto Teófilo Hernando de I+D del Medicamento”, Drug Discovery (ITH), one of the 12 research institutes of Universidad Autonóma de Madrid (UAM), Madrid, Spain. UAM is a 50 year-old young Spanish university that together with various research institutes of the Spanish Research Council (“Consejo Superior de Investigaciones Científicas”), has developed one of the most excellent and competitive science centres in Spain, at the Campus of Cantoblanco, North of Madrid.
IFTH and ITH closely cooperate in the search of a small brain-permeant molecule endowed with neuroprotective properties, to delay disease progression mainly in Alzheimer’s disease, amyotrophic lateral sclerosis and other neurodegenerative diseases.