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Phosphodiesterase 7 Regulation in Cellular and Rodent Models of Parkinson's Disease.

Morales-Garcia JA, Alonso-Gil S, Santos Á, Perez-Castillo A.

Mol Neurobiol. 2019 Aug 31. doi: 10.1007/s12035-019-01745-z. [Epub ahead of print]


Novel Approaches for the Treatment of Alzheimer's and Parkinson's Disease.

Van Bulck M, Sierra-Magro A, Alarcon-Gil J, Perez-Castillo A, Morales-Garcia JA.

Int J Mol Sci. 2019 Feb 8;20(3). pii: E719. doi: 10.3390/ijms20030719. Review.


Neurogenic and neuroprotective donepezil-flavonoid hybrids with sigma-1 affinity and inhibition of key enzymes in Alzheimer's disease.

Estrada Valencia M, Herrera-Arozamena C, de Andrés L, Pérez C, Morales-García JA, Pérez-Castillo A, Ramos E, Romero A, Viña D, Yáñez M, Laurini E, Pricl S, Rodríguez-Franco MI.

Eur J Med Chem. 2018 Aug 5;156:534-553. doi: 10.1016/j.ejmech.2018.07.026. Epub 2018 Jul 11.


Biological and Pharmacological Characterization of Benzothiazole-Based CK-1δ Inhibitors in Models of Parkinson's Disease.

Morales-Garcia JA, Salado IG, Sanz-San Cristobal M, Gil C, Pérez-Castillo A, Martínez A, Pérez DI.

ACS Omega. 2017 Aug 31;2(8):5215-5220. doi: 10.1021/acsomega.7b00869. Epub 2017 Aug 30.


CCAAT/Enhancer binding protein β silencing mitigates glial activation and neurodegeneration in a rat model of Parkinson's disease.

Morales-Garcia JA, Gine E, Hernandez-Encinas E, Aguilar-Morante D, Sierra-Magro A, Sanz-SanCristobal M, Alonso-Gil S, Sanchez-Lanzas R, Castaño JG, Santos A, Perez-Castillo A.

Sci Rep. 2017 Oct 19;7(1):13526. doi: 10.1038/s41598-017-13269-4.


The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro.

Morales-García JA, de la Fuente Revenga M, Alonso-Gil S, Rodríguez-Franco MI, Feilding A, Perez-Castillo A, Riba J.

Sci Rep. 2017 Jul 13;7(1):5309. doi: 10.1038/s41598-017-05407-9.


Subtly Modulating Glycogen Synthase Kinase 3 β: Allosteric Inhibitor Development and Their Potential for the Treatment of Chronic Diseases.

Palomo V, Perez DI, Roca C, Anderson C, Rodríguez-Muela N, Perez C, Morales-Garcia JA, Reyes JA, Campillo NE, Perez-Castillo AM, Rubin LL, Timchenko L, Gil C, Martinez A.

J Med Chem. 2017 Jun 22;60(12):4983-5001. doi: 10.1021/acs.jmedchem.7b00395. Epub 2017 Jun 6.


Pharmacological tools based on imidazole scaffold proved the utility of PDE10A inhibitors for Parkinson's disease.

García AM, Salado IG, Perez DI, Brea J, Morales-García JA, González-García A, Cadavid MI, Loza MI, Luque FJ, Perez-Castillo A, Martinez A, Gil C.

Future Med Chem. 2017 May;9(8):731-748. doi: 10.4155/fmc-2017-0005. Epub 2017 May 9.


The CB1 receptor is required for the establishment of the hyperlocomotor phenotype in developmentally-induced hypothyroidism in mice.

Giné E, Echeverry-Alzate V, Lopez-Moreno JA, Rodriguez de Fonseca F, Perez-Castillo A, Santos A.

Neuropharmacology. 2017 Apr;116:132-141. doi: 10.1016/j.neuropharm.2016.12.018. Epub 2016 Dec 23.


Complement component 3 (C3) expression in the hippocampus after excitotoxic injury: role of C/EBPβ.

Hernandez-Encinas E, Aguilar-Morante D, Morales-Garcia JA, Gine E, Sanz-SanCristobal M, Santos A, Perez-Castillo A.

J Neuroinflammation. 2016 Oct 21;13(1):276.


Phosphodiesterase7 Inhibition Activates Adult Neurogenesis in Hippocampus and Subventricular Zone In Vitro and In Vivo.

Morales-Garcia JA, Echeverry-Alzate V, Alonso-Gil S, Sanz-SanCristobal M, Lopez-Moreno JA, Gil C, Martinez A, Santos A, Perez-Castillo A.

Stem Cells. 2017 Feb;35(2):458-472. doi: 10.1002/stem.2480. Epub 2016 Sep 16.


New neurogenic lipoic-based hybrids as innovative Alzheimer's drugs with σ-1 agonism and β-secretase inhibition.

Estrada M, Pérez C, Soriano E, Laurini E, Romano M, Pricl S, Morales-García JA, Pérez-Castillo A, Rodríguez-Franco MI.

Future Med Chem. 2016 Jul;8(11):1191-207. doi: 10.4155/fmc-2016-0036. Epub 2016 Jul 12.


New cinnamic - N-benzylpiperidine and cinnamic - N,N-dibenzyl(N-methyl)amine hybrids as Alzheimer-directed multitarget drugs with antioxidant, cholinergic, neuroprotective and neurogenic properties.

Estrada M, Herrera-Arozamena C, Pérez C, Viña D, Romero A, Morales-García JA, Pérez-Castillo A, Rodríguez-Franco MI.

Eur J Med Chem. 2016 Oct 4;121:376-386. doi: 10.1016/j.ejmech.2016.05.055. Epub 2016 May 25.


3,4-Dihydro-1,3,5-triazin-2(1H)-ones as the First Dual BACE-1/GSK-3β Fragment Hits against Alzheimer's Disease.

Prati F, De Simone A, Armirotti A, Summa M, Pizzirani D, Scarpelli R, Bertozzi SM, Perez DI, Andrisano V, Perez-Castillo A, Monti B, Massenzio F, Polito L, Racchi M, Sabatino P, Bottegoni G, Martinez A, Cavalli A, Bolognesi ML.

ACS Chem Neurosci. 2015 Oct 21;6(10):1665-82. doi: 10.1021/acschemneuro.5b00121. Epub 2015 Aug 3.


Novel N-Acetyl Bioisosteres of Melatonin: Melatonergic Receptor Pharmacology, Physicochemical Studies, and Phenotypic Assessment of Their Neurogenic Potential.

de la Fuente Revenga M, Fernández-Sáez N, Herrera-Arozamena C, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, Caignard DH, Rivara S, Rodríguez-Franco MI.

J Med Chem. 2015 Jun 25;58(12):4998-5014. doi: 10.1021/acs.jmedchem.5b00245. Epub 2015 Jun 10.


PDE7 inhibitor TC3.6 ameliorates symptomatology in a model of primary progressive multiple sclerosis.

Mestre L, Redondo M, Carrillo-Salinas FJ, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, Gil C, Martínez A, Guaza C.

Br J Pharmacol. 2015 Sep;172(17):4277-90. doi: 10.1111/bph.13192. Epub 2015 Jul 14.


Phosphodiesterase 7 inhibition induces dopaminergic neurogenesis in hemiparkinsonian rats.

Morales-Garcia JA, Alonso-Gil S, Gil C, Martinez A, Santos A, Perez-Castillo A.

Stem Cells Transl Med. 2015 Jun;4(6):564-75. doi: 10.5966/sctm.2014-0277. Epub 2015 Apr 29.


Neurogenic Potential Assessment and Pharmacological Characterization of 6-Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin-Pinoline Hybrids.

de la Fuente Revenga M, Pérez C, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, Caignard DH, Yáñez M, Gamo AM, Rodríguez-Franco MI.

ACS Chem Neurosci. 2015 May 20;6(5):800-10. doi: 10.1021/acschemneuro.5b00041. Epub 2015 Apr 9.


CCAAT/enhancer binding protein β directly regulates the expression of the complement component 3 gene in neural cells: implications for the pro-inflammatory effects of this transcription factor.

Hernandez-Encinas E, Aguilar-Morante D, Cortes-Canteli M, Morales-Garcia JA, Gine E, Santos A, Perez-Castillo A.

J Neuroinflammation. 2015 Jan 24;12:14. doi: 10.1186/s12974-014-0223-2.


Multitarget drug discovery for Alzheimer's disease: triazinones as BACE-1 and GSK-3β inhibitors.

Prati F, De Simone A, Bisignano P, Armirotti A, Summa M, Pizzirani D, Scarpelli R, Perez DI, Andrisano V, Perez-Castillo A, Monti B, Massenzio F, Polito L, Racchi M, Favia AD, Bottegoni G, Martinez A, Bolognesi ML, Cavalli A.

Angew Chem Int Ed Engl. 2015 Jan 26;54(5):1578-82. doi: 10.1002/anie.201410456. Epub 2014 Dec 11.


Silencing phosphodiesterase 7B gene by lentiviral-shRNA interference attenuates neurodegeneration and motor deficits in hemiparkinsonian mice.

Morales-Garcia JA, Aguilar-Morante D, Hernandez-Encinas E, Alonso-Gil S, Gil C, Martinez A, Santos A, Perez-Castillo A.

Neurobiol Aging. 2015 Feb;36(2):1160-73. doi: 10.1016/j.neurobiolaging.2014.10.008. Epub 2014 Oct 13.


Modulation of cAMP-specific PDE without emetogenic activity: new sulfide-like PDE7 inhibitors.

García AM, Brea J, Morales-García JA, Perez DI, González A, Alonso-Gil S, Gracia-Rubio I, Ros-Simó C, Conde S, Cadavid MI, Loza MI, Perez-Castillo A, Valverde O, Martinez A, Gil C.

J Med Chem. 2014 Oct 23;57(20):8590-607. doi: 10.1021/jm501090m. Epub 2014 Oct 8.


New melatonin-N,N-dibenzyl(N-methyl)amine hybrids: potent neurogenic agents with antioxidant, cholinergic, and neuroprotective properties as innovative drugs for Alzheimer's disease.

López-Iglesias B, Pérez C, Morales-García JA, Alonso-Gil S, Pérez-Castillo A, Romero A, López MG, Villarroya M, Conde S, Rodríguez-Franco MI.

J Med Chem. 2014 May 8;57(9):3773-85. doi: 10.1021/jm5000613. Epub 2014 Apr 28.


Crosstalk between phosphodiesterase 7 and glycogen synthase kinase-3: two relevant therapeutic targets for neurological disorders.

Morales-Garcia JA, Palomo V, Redondo M, Alonso-Gil S, Gil C, Martinez A, Perez-Castillo A.

ACS Chem Neurosci. 2014 Mar 19;5(3):194-204. doi: 10.1021/cn400166d. Epub 2014 Jan 17.


Glycogen synthase kinase-3 inhibitors as potent therapeutic agents for the treatment of Parkinson disease.

Morales-García JA, Susín C, Alonso-Gil S, Pérez DI, Palomo V, Pérez C, Conde S, Santos A, Gil C, Martínez A, Pérez-Castillo A.

ACS Chem Neurosci. 2013 Feb 20;4(2):350-60. doi: 10.1021/cn300182g. Epub 2012 Dec 5.


Glycogen synthase kinase 3 inhibition promotes adult hippocampal neurogenesis in vitro and in vivo.

Morales-Garcia JA, Luna-Medina R, Alonso-Gil S, Sanz-Sancristobal M, Palomo V, Gil C, Santos A, Martinez A, Perez-Castillo A.

ACS Chem Neurosci. 2012 Nov 21;3(11):963-71. doi: 10.1021/cn300110c. Epub 2012 Sep 24.


Microwave-assisted synthesis of hydroxyphenyl nitrones with protective action against oxidative stress.

Chavarría C, Perez DI, Pérez C, Morales Garcia JA, Alonso-Gil S, Pérez-Castillo A, Gil C, Souza JM, Porcal W.

Eur J Med Chem. 2012 Dec;58:44-9. doi: 10.1016/j.ejmech.2012.09.044. Epub 2012 Oct 5.


Developmentally-induced hypothyroidism alters the expression of Egr-1 and Arc genes and the sensitivity to cannabinoid agonists in the hippocampus. Possible implications for memory and learning.

Giné E, Echeverry-Alzate V, López-Moreno JA, López-Jimenez A, Torres-Romero D, Perez-Castillo A, Santos A.

Mol Cell Endocrinol. 2013 Jan 5;365(1):119-28. doi: 10.1016/j.mce.2012.10.004. Epub 2012 Oct 16.


The new iminothiadiazole derivative VP1.14 ameliorates hippocampal damage after an excitotoxic injury.

Susín C, Morales-Garcia JA, Aguilar-Morante D, Palomo V, Sanz-Sancristobal M, Alonso-Gil S, Gil C, Santos A, Martinez A, Perez-Castillo A.

J Neurochem. 2012 Sep;122(6):1193-202. doi: 10.1111/j.1471-4159.2012.07866.x. Epub 2012 Aug 3.


Effect of phosphodiesterase 7 (PDE7) inhibitors in experimental autoimmune encephalomyelitis mice. Discovery of a new chemically diverse family of compounds.

Redondo M, Brea J, Perez DI, Soteras I, Val C, Perez C, Morales-García JA, Alonso-Gil S, Paul-Fernandez N, Martin-Alvarez R, Cadavid MI, Loza MI, Perez-Castillo A, Mengod G, Campillo NE, Martinez A, Gil C.

J Med Chem. 2012 Apr 12;55(7):3274-84. doi: 10.1021/jm201720d. Epub 2012 Mar 16.


5-imino-1,2,4-thiadiazoles: first small molecules as substrate competitive inhibitors of glycogen synthase kinase 3.

Palomo V, Perez DI, Perez C, Morales-Garcia JA, Soteras I, Alonso-Gil S, Encinas A, Castro A, Campillo NE, Perez-Castillo A, Gil C, Martinez A.

J Med Chem. 2012 Feb 23;55(4):1645-61. doi: 10.1021/jm201463v. Epub 2012 Feb 3.


Neuroprotective efficacy of quinazoline type phosphodiesterase 7 inhibitors in cellular cultures and experimental stroke model.

Redondo M, Zarruk JG, Ceballos P, Pérez DI, Pérez C, Perez-Castillo A, Moro MA, Brea J, Val C, Cadavid MI, Loza MI, Campillo NE, Martínez A, Gil C.

Eur J Med Chem. 2012 Jan;47(1):175-85. doi: 10.1016/j.ejmech.2011.10.040. Epub 2011 Nov 4.


Role of C/EBPβ transcription factor in adult hippocampal neurogenesis.

Cortes-Canteli M, Aguilar-Morante D, Sanz-Sancristobal M, Megias D, Santos A, Perez-Castillo A.

PLoS One. 2011;6(10):e24842. doi: 10.1371/journal.pone.0024842. Epub 2011 Oct 7.


Phosphodiesterase 7 inhibition preserves dopaminergic neurons in cellular and rodent models of Parkinson disease.

Morales-Garcia JA, Redondo M, Alonso-Gil S, Gil C, Perez C, Martinez A, Santos A, Perez-Castillo A.

PLoS One. 2011 Feb 24;6(2):e17240. doi: 10.1371/journal.pone.0017240.


Decreased CCAAT/enhancer binding protein β expression inhibits the growth of glioblastoma cells.

Aguilar-Morante D, Cortes-Canteli M, Sanz-Sancristobal M, Santos A, Perez-Castillo A.

Neuroscience. 2011 Mar 10;176:110-9. doi: 10.1016/j.neuroscience.2010.12.025. Epub 2010 Dec 23.


Peroxisome proliferator-activated receptor γ ligands regulate neural stem cell proliferation and differentiation in vitro and in vivo.

Morales-Garcia JA, Luna-Medina R, Alfaro-Cervello C, Cortes-Canteli M, Santos A, Garcia-Verdugo JM, Perez-Castillo A.

Glia. 2011 Feb;59(2):293-307. doi: 10.1002/glia.21101.


Inhibition of glioblastoma growth by the thiadiazolidinone compound TDZD-8.

Aguilar-Morante D, Morales-Garcia JA, Sanz-SanCristobal M, Garcia-Cabezas MA, Santos A, Perez-Castillo A.

PLoS One. 2010 Nov 8;5(11):e13879. doi: 10.1371/journal.pone.0013879.


Developmental hypothyroidism increases the expression of kainate receptors in the hippocampus and the sensitivity to kainic acid-induced seizures in the rat.

Giné E, Morales-Garcia JA, Perez-Castillo A, Santos A.

Endocrinology. 2010 Jul;151(7):3267-76. doi: 10.1210/en.2010-0070. Epub 2010 Apr 21.


15-Deoxi-Delta(12,14)-prostaglandin J2 is a tubulin-binding agent that destabilizes microtubules and induces mitotic arrest.

Cocca C, Dorado J, Calvo E, López JA, Santos A, Perez-Castillo A.

Biochem Pharmacol. 2009 Nov 15;78(10):1330-9. doi: 10.1016/j.bcp.2009.06.100. Epub 2009 Jul 1.


Anticonvulsant and neuroprotective effects of the novel calcium antagonist NP04634 on kainic acid-induced seizures in rats.

Morales-Garcia JA, Luna-Medina R, Martinez A, Santos A, Perez-Castillo A.

J Neurosci Res. 2009 Dec;87(16):3687-96. doi: 10.1002/jnr.22165.


[Physicochemical water quality index, a management tool for tropical-flooding lagoons].

Pérez-Castillo AG, Rodríguez A.

Rev Biol Trop. 2008 Dec;56(4):1905-18. Spanish.


Hypothyroidism decreases the biogenesis in free mitochondria and neuronal oxygen consumption in the cerebral cortex of developing rats.

Martinez B, Rodrigues TB, Gine E, Kaninda JP, Perez-Castillo A, Santos A.

Endocrinology. 2009 Aug;150(8):3953-9. doi: 10.1210/en.2008-1755. Epub 2009 Apr 23.


Synthesis, structural analysis, and biological evaluation of thioxoquinazoline derivatives as phosphodiesterase 7 inhibitors.

Castaño T, Wang H, Campillo NE, Ballester S, González-García C, Hernández J, Pérez C, Cuenca J, Pérez-Castillo A, Martínez A, Huertas O, Gelpí JL, Luque FJ, Ke H, Gil C.

ChemMedChem. 2009 May;4(5):866-76. doi: 10.1002/cmdc.200900043.


Cancer stem cells and brain tumors.

Pérez Castillo A, Aguilar-Morante D, Morales-García JA, Dorado J.

Clin Transl Oncol. 2008 May;10(5):262-7. Review.


CCAAT/enhancer binding protein beta deficiency provides cerebral protection following excitotoxic injury.

Cortes-Canteli M, Luna-Medina R, Sanz-Sancristobal M, Alvarez-Barrientos A, Santos A, Perez-Castillo A.

J Cell Sci. 2008 Apr 15;121(Pt 8):1224-34. doi: 10.1242/jcs.025031.


Implication of the endocannabinoid system in the locomotor hyperactivity associated with congenital hypothyroidism.

Asúa T, Bilbao A, Gorriti MA, Lopez-Moreno JA, Del Mar Alvarez M, Navarro M, Rodríguez de Fonseca F, Perez-Castillo A, Santos A.

Endocrinology. 2008 May;149(5):2657-66. doi: 10.1210/en.2007-1586. Epub 2008 Jan 24.


NP031112, a thiadiazolidinone compound, prevents inflammation and neurodegeneration under excitotoxic conditions: potential therapeutic role in brain disorders.

Luna-Medina R, Cortes-Canteli M, Sanchez-Galiano S, Morales-Garcia JA, Martinez A, Santos A, Perez-Castillo A.

J Neurosci. 2007 May 23;27(21):5766-76.


The spot 14 protein inhibits growth and induces differentiation and cell death of human MCF-7 breast cancer cells.

Sanchez-Rodriguez J, Kaninda-Tshilumbu JP, Santos A, Perez-Castillo A.

Biochem J. 2005 Aug 15;390(Pt 1):57-65.


Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation.

Luna-Medina R, Cortes-Canteli M, Alonso M, Santos A, Martínez A, Perez-Castillo A.

J Biol Chem. 2005 Jun 3;280(22):21453-62. Epub 2005 Apr 6.

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