Neuroregenerative Chemistry

Neuroregenerative Chemistry

Neuroregenerative Chemistry

 

Principal investigator: Ernesto Doncel Perez, Ph.D.

E-mail: ernestod@sescam.jccm.es

 

Our group has been founded in 2008 with the main research interest centered upon regeneration and repair of a injured central nervous system (CNS). Within this broad field we particularly focus on control of the glial scar formation and promotion of neural/axonal growth in the damaged area.  To accomplish these objectives we opt for a chemical approach that includes new drugs development, their de novo chemical synthesis and a biological evaluation of their effectiveness. In addition, we study bio-compatible and bio-degradable polymers and their potential as vehicles for drug delivery and/or possible substrates for cellular transplants. Important part of our effort is also dedicated to design, synthesis and evaluation of compounds that allow for controlled proliferation and differentiation of mammalian neural precursors. Recently we and our collaborators described new biomarkers for Guillain Barré Syndrome, and we still go ahead with this study.

 

In the laboratory we employ methodologies stemming from organic chemistry, cellular and molecular biology as well as animal models of the CNS pathologies (especially in spinal cord injury and peripheral neuropathy) pursuing the development of compounds that may be transferred to the clinic and used effectively as therapies in patients with spinal cord lesions and other pathologies of the CNS.

 

 

Personnel

 

Ernesto Doncel Pérez: Ph.D. in Molecular and Cellular Biology (UAM).

 

Dr. Javier Blanco García: M.D. in Surgery and Medicine (UCM).

 

Carmen Fernández: Clinical Psychologist (Comillas University, Madrid).

 

Vinnitsa Buzoianu: Ph.D. in Biological Sciences. (Universidad Nacional Autónoma de México).

 

Raquel Díaz Martínez. Ph.D. in Biological Sciences. (UAM).

 

Alejandro Arriero. Biochemist (UCLM).Neurosciences Master student in practices (UCM).

 

 

 

Selected publications

 

- Vinnitsa Buzoianu-Anguiano, Mabel Torres-Llacsa and Ernesto Doncel-Pérez*. Role of Aldynoglia Cells in Neuroinflammatory and Neuroimmune Responses after Spinal Cord Injury Cells 2021, 10, 2783. https://doi.org/10.3390/ cells10102783

 

- De la Fuente J, Urra JM, Contreras M, Pacheco I, Ferreras-Colino E, Doncel-Pérez E, Fernández de Mera IG, Villar M, Cabrera CM, Gómez Hernando C, Vargas Baquero E, Blanco García J, Rodríguez Gómez J, Velayos Galán A, Feo Brito F, Gómez Torrijos E, Cabezas-Cruz A, Gortázar C. A data set for the analysis of antibody response to glycan alpha-Gal in individuals with immune-mediated disorders. F1000Res. 2020 Nov 24;9:1366. doi: 10.12688/f1000research.27495.2. eCollection 2020.PMID: 34408852 Free PMC article.

 

- De la Fuente J, Armas O, Sánchez-Rodríguez L, Gortázar C, Lukashev AN; Doncel-Pérez E in COVID-BCG Collaborative Working Group . Citizen science initiative points at childhood BCG vaccination as a risk factor for COVID-19. TransboundEmerg Dis. 2021 Apr 7:10.1111/tbed.14097. doi: 10.1111/tbed.14097. Online ahead of print.PMID: 33825348 Free PMC article.

 

- Pacheco I, Fernández de Mera IG, FeoBrito F, Gómez Torrijos E, Villar M, Contreras M, Lima-Barbero JF, Doncel-Pérez E, Cabezas-Cruz A, Gortázar C, de la Fuente J. Characterization of the anti-α-Gal antibody profile in association with Guillain-Barré syndrome, implications for tick-related allergic reactions. Ticks Tick Borne Dis. 2021 May;12(3):101651. doi: 10.1016/j.ttbdis.2021.101651. Epub 2021 Jan 11. PMID: 33465663 Free article.

 

- Doncel-Pérez E.; Marinela Contreras; Cesar Gómez Hernando; Eduardo Vargas; Javier Blanco; Javier Rodríguez; Alberto Velayos; Alejandro Cabezas-Cruz; Christian Gortazar; José de la Fuente. “What is the impact of the antibody response to glycan alpha-Gal in Guillain-Barré syndrome associated with SARS-CoV-2 infection? MERIT RESEARCH JOURNAL OF MEDICINE AND MEDICAL SCIENCES s (ISSN: 2354-323X) Vol. 8(11) pp. 730-737, November, 2020.

 

- Revuelta J, Aranaz I, Acosta N, Civera C, Bastida A, Peña N, Monterrey DT, Doncel-Pérez E, Garrido L, Heras Á, García-Junceda E, Fernández-Mayoralas A. Unraveling the Structural Landscape of Chitosan-Based Heparan Sulfate Mimics Binding to Growth Factors: Deciphering Structural Determinants for Optimal Activity. ACS Appl Mater Interfaces. 2020 Jun 10;12(23):25534-25545.

 

- Raúl Benito-Arenas, Ernesto Doncel-Pérez, Mar Fernández Gutiérrez, Leoncio Garrido, Eduardo García-Junceda, Julia Revuelta, Agatha Bastida. A holistic approach to unravelling chondroitin sulfation: Correlations between surface charge, structure and binding to growth factors. Carbohydr Polym. 2018 Dec 15;  202: 211-218.

 

- Doncel-Pérez E, Ellis G, Sandt C, Shuttleworth PS, Bastida A, Revuelta J, García-Junceda E, Fernández-Mayoralas A, Garrido L. Biochemical profiling of rat embryonic stem cells grown on electrospun polyester fibers using synchrotron infrared microspectroscopy. Anal Bioanal Chem. 2018 Jun;410(16):3649-3660.

 

- Doncel-Pérez E, Aranaz I, Bastida A, Revuelta J, Camacho C, Acosta N, Garrido L, Civera C, García-Junceda E, Heras A, Fernández-Mayoralas A. Synthesis, physicochemical characterization and biological evaluation of chitosan sulfate as heparan sulfate mimics. Carbohydr Polym. 2018 Jul 1;191:225-233.

 

- Mateos-Hernández L, Villar M, Doncel-Pérez E, Trevisan-Herraz M, García-Forcada Á, Ganuza FR, Vázquez J, de la Fuente J. Quantitative proteomics reveals Piccolo as a candidate serological correlate of recovery from Guillain-Barré syndrome. Oncotarget. 2016 Nov 15;7(46):74582-74591.

 

- Doncel-Pérez E, Mateos-Hernández L, Pareja E, García-Forcada Á, Villar M, Tobes R, Romero Ganuza F, Vila Del Sol V, Ramos R, Fernández de Mera IG, de la Fuente J. Expression of Early Growth Response Gene-2 and Regulated Cytokines Correlates with Recovery from Guillain-Barré Syndrome. J Immunol. 2016  Feb 1;196(3):1102-7

 

- García-Álvarez I, Fernández-Mayoralas A, Moreno-Lillo S, Sánchez-Sierra M, Nieto-Sampedro M, Doncel-Pérez E. Inhibition of glial proliferation, promotion of axonal growth and myelin production by synthetic glycolipid: A new approach for spinal cord injury treatment. Restor Neurol Neurosci. 2015;33(6):895-910.

 

- Sánchez-Sierra M, García-Álvarez I, Fernández-Mayoralas A, Moreno-Lillo S, Barroso García G, Moral Dardé V, Doncel-Pérez E. Mass Spectrometry in Pharmacokinetic Studies of a Synthetic Compound for Spinal Cord Injury Treatment. Biomed Res Int. 2015; 2015:169234.

 

- Serrano-Pérez MC, Fernández M, Neria F, Berjón-Otero M, Doncel-Pérez E, Cano E, Tranque P. NFAT transcription factors regulate survival, proliferation, migration, and differentiation of neural precursor cells. Glia. 2015 Jun;63(6):987-1004.

 

- Doncel-Pérez E, García-Álvarez I, Fernández-Mayoralas A, Nieto-Sampedro M. Synthetic glycolipids for glioma growth inhibition developed from neurostatin and NF115 compound. Bioorg Med Chem Lett. 2013 Jan 15;23(2):435-9.

 

- Muñetón-Gómez VC, Doncel-Pérez E, Fernandez AP, Serrano J, Pozo-Rodrigálvarez A, Vellosillo-Huerta L, Taylor JS, Cardona-Gómez GP, Nieto-Sampedro M, Martínez-Murillo R. Neural differentiation of transplanted neural stem cells in a rat model of striatal lacunar infarction: light and electron microscopic observations. Front Cell Neurosci. 2012 Aug 2;6:30.

 

- Doncel-Pérez E, Caballero-Chacón S, Nieto-Sampedro M. Neurosphere cell differentiation to aldynoglia promoted by olfactory ensheathing cell conditioned medium. Glia. 2009 Oct;57(13):1393-409.

 

 

 

Biobank, Patent and Useful model

 

BIOBANK: The processed blood samples from voluntary donors performing the Guillaín-Barré Syndrome Collection, this is managed and conserved in the Neuroregenerative Chemistry Lab. The GBS collection belongs to BioBank of Hospital Virgen de la Salud, Toledo (BioB-HVS). Register Nº 241/2018,  Exp. 4500038/0004042 in Centros, Servicios y Establecimientos Sanitarios, Consejería de Sanidad Castilla La-Mancha.

 

 

PATENT: Use of sulfated glycolipids as compunds that promote neurite growth and myelinization and inhibit the proliferation of astroglia and microglia. (WO2014006250). INVENTORS: E Doncel-Pérez, I García Álvarez, A Fernández-Mayoralas, M Nieto-Sampedro. INTELECTUAL PROPERTY HOLDER: The National Council for Scientific Research (CSIC, Madrid) and National Hospital for Paraplegics (HNP, Toledo).

 

 

MODEL: Use of murine GFP-positive neuronal stem cells as experimental cell transplants in the mammalian central nervous system. INVENTORS: E Doncel-Pérez ¬ Manuel Nieto-Sampedro.

The use licence managed by the CSIC´s office for knowledge transfer (The licence Ref: GLIA 57:1393–1409; 2009).

 

 

 

Research Lines

 

- Creation of new drugs, starting with their chemical synthesis, that can be used as promoters of neuronal regeneration and/or inhibitors of the glial scar formation. Subsequent evaluation of these new drugs in neural cell cultures (i.e. neurons, astrocytes and oligodendrocytes) and spinal contusion model in the adult rat . This line is being realized in collaboration with the Institute for Organic Chemistry (IQO at the CSIC).
 

- Biological testing of bio-compatible and bio-degradable polymers for their use as cellular therapies, delivery vehicles and/or substrates for neural stem cells.. This line is being realized in collaboration with the Institute for Polymers Science and Technology (ICTP) and IQO at the CSIC, Pharmacy Faculty at Universidad Complutense of Madrid.
 

- Chemical synthesis of molecules that can be employed in controlled expansion and differentiation of neural stem cells, in collaboration with IQO at the CSIC.
 

- Predictors and biomarkers for peripheral autoimmune neuropathies: Description and study of their pathophysiological role (In collaboration with SaBio Group, IREC, UCLM).
 

 

 

Projects

 

1) New strategies for the repair of injured spinal cord: Allogenic transplantation of mesenchymal or neural precursor cells, predegenerated peripheral nerve graft in combination with synthetic inhibitor of astroglia and microglia.

PIs (at HNP): Vinnitsa Buzoianu, Ernesto Doncel-Pérez. Financed by CONACYT, México (2021-2022).

 

 

2) Tailor-made chitosans: From sustainable polymer synthesis to smart materials design for biomedical applications.A coordinated project between CSIC, UCM andNational Hospital for Paraplegics.

Collaborator at HNP: Ernesto Doncel-Pérez.Financed by the Ministry of Science, Innnovation and Universities.

 

 

3) Functionalized hydrogels with modified glycosaminoglycans: preparation and study of their properties in neural cells and tissues. A joint project between the CSIC and National Hospital for Paraplegics (MAT2015-65184-C2-2-R).

Collaborator at HNP: Ernesto Doncel-Pérez. Financed by the Ministry of Economy and Competitiveness (2016 – 2019).

 

 

4) Validation of blood biomarkers for Guillain-Barré Syndrome.

PI (at HNP): Ernesto Doncel-Pérez; requested funding to Merck(2017-2018).

 

 

5) Neurofunctional evaluation of multi-component systems for the promotion of axonal growth and mielinization in injured spinal cord. Joint project between the CSIC and National Hospital for Paraplegics (Ref: PI11/00592).

PI (at HNP): Ernesto Doncel-Pérez. Financed by the the Ministry of Economy and Competitiveness, Institute Carlos the III (2012-2015)

 

 

6) Synthesis of glycopolimers mimetic of  heparan- and chondroitin sulfate for stem cell therapy following spinal cord injuries. Collaborative project with the Institutes for Organic Chemistry and Institute for Polymers Science and Technology at the CSIC).

PI (at HNP): Ernesto Doncel-Pérez; Financed by MAPFRE (2012-2013).

 

 

7) Neural stem cells and new synthetic glycolipids for regenerataion of the injured spinal cord.

PI: Ernesto Doncel Pérez. Financed by FISCAM, SESCAM (2011-2013).