Molecular Neuroprotection

Molecular Neuroprotection

Molecular Neuroprotection

 

Principal investigators:  Dr. Rodrigo Maza, Dr. Manuel Nieto

E-mail: rodrigom@sescam.jccm.es  mnietod@sescam.jccm.es

Facebook: https://www.facebook.com/neuroproteccion.medula.espinal

 

We are a group of biologists and pharmacists focused on the development of pharmacological and genetic therapies for the treatment of spinal cord injury. The laboratory employs a wide range of molecular, histological, behavioural, and bioinformatics techniques that allow the comprehensive study of the processes involved in spinal cord injury and its treatments. Our location at the Hospital Nacional de Parapléjicos de Toledo provides us with direct contact with clinical reality, which favours the translation of results and direct knowledge of the reality and needs of patients.

Our team:

Rodrigo Martínez Maza: Principal Investigator; PhD in Biology.

 Manuel Nieto Díaz: Principal Investigator; PhD in Biology.

 David Reigada Prado: Postdoctoral Researcher; PhD in Biology.

 Teresa Muñoz de Galdeano: Postdoctoral Researcher; PhD in Pharmacy.

 Mª Asunción de la Barreda Manso: Postdoctoral Researcher; PhD in Biology.

 Altea Soto Neira: PhD student. Bachelor's degree in Biology.

E-mails: rodrigom@sescam.jccm.es, mnietod@sescam.jccm.es

Facebook: https://www.facebook.com/neuroproteccion.medula.espinal/  

Specialisation (UNESCO code): 320101, 320711, 2415

 

The main objectives of the Molecular Neuroprotection Group are:

 

1) To characterise at the molecular and cellular level the deleterious mechanisms triggered in neurodegenerative processes, in particular spinal cord injury (SCI);

 2) To develop and evaluate neuroprotective therapies to reduce the deleterious effects of spinal cord injury.

Our group currently maintains active lines of research aimed at:

 

1) the evaluation of the modulation of microRNAs as a therapeutic treatment to modulate cell death processes after spinal cord trauma. This is currently the central line of the group, with studies focusing on miR-138-5p and their effects on apoptosis, miR-199a-5p on autophagy, and miR-135a-5p on purinergic system-mediated excitotoxicity. On the occasion of the COVID-19 pandemic, the group used its expertise and microRNA analysis tools to evaluate the therapeutic potential of these molecules in the treatment of SARS-CoV-2 infection;

2) the development and validation of safe, effective, and translatable tools for the controlled administration of microRNAs for the treatment of spinal cord injury. To this end, we have established collaborations with experts in nucleic acid chemistry from the department of Química de Ácidos Nucleicos, Instituto de Química Avanzada de Cataluña (IQAC, CSIC) and experts in the synthesis, characterisation and functionalisation of polymeric biomaterials from the Grupo de Funcionalización de Polímeros del Instituto de Ciencia y Tecnología de Polímeros (ICTP, CSIC). 

We also maintain other lines and collaborations in different fields including:

3) the modulation of central fatigue after spinal cord injury and other pathologies of the nervous system. This line focuses on the evaluation of the drug Rimonabant, an inverse agonist/antagonist of the cannabinoid CB1 receptor, in animal models of spinal cord injury;

4) the application of microRNAs, specifically miR-199, as a therapeutic and diagnostic tool in gynaecological cancers;

5) evaluation of the therapeutic potential of modulation of the purinergic system in the treatment of secondary damage in spinal cord trauma;

6) characterisation of programmed cell death processes (non-apoptotic) following spinal cord injury;

7) the development and evaluation of tools and procedures for the implementation of hospital 3D printing as an approximation to the use of 3D printing in the treatment of spinal cord injury;

8) the development of computer support tools to acquire, analyse and share information in spinal cord injury experiments. This line is carried out in collaboration with the Instituto de Informática de Albacete (I3A) and has begun with the development of an App for mobiles/tablets capable of recording and storing motor behaviour information in mice. Recently, a project has been started on a repository of images of injured spinal cords with comparative analysis methods and results identifying which neurons are lost after spinal cord injury at different times;

9) the study of nerve regeneration in deer antlers: identification of neuroprotective and neuroregenerating mechanisms with potential clinical application in a model of rapid axonal regeneration and growth in adult mammals;

10) the evaluation of changes in the expression and activity of several lipid molecules, such as sphingosine 1-phosphate, a regulator of cell death, regeneration, and glial reactivity.

Projects with active funding

  • “Adaptación al ámbito clínico de un sistema de herramientas terapéuticas personalizables para el tratamiento de la lesión medular combinando hipotermia y terapia de ARN”. Funded by Consejería de Educación, Junta de Comunidades de Castilla La Mancha (2022-2025). PIs: Teresa Muñoz de Galdeano and Manuel Nieto Díaz.
  • “Desarrollo y fabricación de hisopos por impresión 3D para la elaboración de kits de extracción de muestras COVID19: validación hospitalaria de su uso”. Funded by Consejo Superior de Investigaciones Científicas (2020-2021). PIs: Juan Rodríguez Hernández and Manuel Nieto-Díaz.
  • “El Rimonabant para la mejora de la capacidad de andar en lesionados medulares”. Funded by por Instituto de Salud Carlos III (2021-2024). PIs: Antonio Oliviero and Manuel Nieto Díaz.
  • “Uso del Rimonabant como tratamiento de la Fatiga central en la lesión medular: ensayos en rata”. Contract with SAMOS Medical Enterprise SLU (2018-2023). PI: Manuel Nieto Díaz.
  • “Terapia basada en microRNAs para atenuar la quimiorresistencia en el cáncer ginecológico”. Funded by la Fundación EuroCaja Rural (2021-2022). PIs: Teresa Muñoz de Galdeano and Rodrigo Martínez Maza.

Publications (last 10 years)

  • Maza RM, Barreda-Manso MA, Reigada D, Silván Á, Muñoz-Galdeano T, ... 2022. MicroRNA-138-5p Targets Pro-Apoptotic Factors and Favors Neural Cell Survival: Analysis in the Injured Spinal Cord. Biomedicines 10 (7), 1559D.
  • Soto A, Nieto-Díaz M, Reigada D, Barreda-Manso MA, ... 2022. MiR-182-5p regulates Nogo-A expression and promotes neurite outgrowth of hippocampal neurons in vitro. Pharmaceuticals 15 (5), 529.
  • Reigada, V Soto, M González-Rodríguez, MA Barreda-Manso, A Soto, .... 2022. Stereological evaluation of tissue preservation after neuroprotective treatments for traumatic spinal cord injury. bioRxiv. 2022.05.05.490720
  • Klionsky DJ, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). 2021. Autophagy 17(1):1-382.
  • Barreda-Manso, M. A., Nieto-Díaz, M., Soto, A., Muñoz-Galdeano, T., Reigada, D., & Maza, R. M. 2021. In Silico and In Vitro Analyses Validate Human MicroRNAs Targeting the SARS-CoV-2 3′-UTR. International Journal of Molecular Sciences 22(11), 6094.
  • Rotondi M, Nieto-Díaz M, Magri F, Oliviero A. 2020. Balancing the need for rapid and rigorous scientific data during early phase of the COVID-19 pandemic: A further role for the scientific community. European Journal of Internal Medicine 77, 152.
  • Merino S, Maza RM, Nieto-Díaz M, Eritja R, Díaz Díaz D. 2019. Alginate hydrogels as scaffolds and delivery systems to repair the damaged spinal cord. Biotechnology Journal 14, 1-8.
  • Reigada D, Calderón-García AÁ, Soto-Catalán M, Nieto-Díaz M, Muñoz-Galdeano T, Del Águila Á, Maza RM. 2019. MicroRNA-135a-5p reduces P2X7 -dependent rise in intracellular calcium and protects against excitotoxicity. Journal Neurochemistry 151 (1), 116-130.
  • Muñoz-Galdeano T, Reigada D, Del Águila Á, Vélez I, Caballero-López MJ, Maza RM, Nieto-Díaz M. 2018. Cell Specific Changes of Autophagy in a Mouse Model of Contusive Spinal Cord Injury. Frontiers in Cellular Neuroscience 12, 164.
  • Gómez A, Nieto-Díaz M, del Águila Á, Arias E. 2018. BAMOS: A recording application for BAsso MOuse Scale of locomotion in experimental models of spinal cord injury. Computers in biology and medicine 96, 32-40
  • Caballero-López MJ, Nieto-Díaz M, Yunta M, Reigada D, Muñoz-Galdeano T, Del Águila Á, Navarro-Ruíz R, Pita-Thomas W, Lindholm D, Maza RM. 2017. XIAP Interacts with and Regulates the Activity of FAF1. Biochim Biophys Acta Molecular Cellular Research, 1864(7), 1335-1348.
  • Reigada, David; Navarro-Ruiz, Rosa María; Caballero-López, Marcos Javier; Del Águila, Ángela; Muñoz-Galdeano, Teresa; Maza, Rodrigo M; Nieto-Díaz, Manuel. 2016. Diadenosine tetraphosphate (Ap4A) inhibits ATP-induced excitotoxicity: a neuroprotective strategy for traumatic spinal cord injury treatment. Purinergic Signalling 13 (1),75-87.
  • Pita-Thomas, Wolfgang; Barroso-García, Gemma; Moral, Verónica; Hackett, Amber R; Cavalli, Valeria; Nieto-Diaz, Manuel. 2016. Identification of axon growth promoters in the secretome of the deer antler velvet. Neuroscience 340,333-344.
  • Reigada D, Nieto-Díaz M, Navarro-Ruiz R, Caballero-López MJ, Del Águila A, Muñoz-Galdeano T, Maza RM. 2015. Acute administration of ucf-101 ameliorates the locomotor impairments induced by a traumatic spinal cord injury. Neuroscience, 300, 404-17.
  • Nieto-Díaz M, Esteban FJ, Reigada D, Muñoz-Galdeano T, Yunta M, Caballero-López M, Navarro-Ruiz R, Del Águila A, Maza RM.2014. MicroRNA dysregulation in spinal cord injury: causes, consequences and therapeutics. Frontiers in Cellular Neuroscience 8, 53.
  • Nieto-Diaz, M.; Pita-Thomas, DW. Muñoz-Galdeano T, Martínez-Maza, C; Navarro-Ruiz, R.; Reigada, D.; Yunta-González M, Caballero-López, MJ.; Nieto-Sampedro, M.; Martínez-Maza, R. 2012. Deer antler innervation and regeneration. Frontiers in Bioscience 17, 1389-1401.
  • Yunta, M.; Nieto-Diaz, M.; Esteban, FJ.; Caballero-López, M.; Navarro-Ruiz, R.; Reigada, D.; Pita-Tomas, DW.; Águila, Á.; Muñoz Galdeano, T. y Maza RM. 2012. Spinal cord injury induces general repression of microRNAs. PLoSOne 7(4), E35434.