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

Specialization (UNESCO code): 320101, 320711, 2415

 

 

The Molecular Neuroprotection Group has as its main objectives:

 

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

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

 

In the first objective, group studies have focused on the characterization of the processes and regulators of apoptosis after spinal cord injury. In recent years, the scope of study has been extended to other forms of cell death and associated processes, such as necroptosis and autophagy. Within the second objective, our work initially focused on the study of the role and therapeutic potential of apoptosis inhibitor proteins (IAPs) on apoptotic processes that are recorded after spinal cord injury. The successive incorporations of researchers into the group opened the range of possible therapies under analysis, incorporating microRNAs - global regulators of gene expression and cell status - or the molecules of the purinergic system.

Currently our group keeps active research lines aimed at:

 

1) evaluation of the modulation of microRNAs as a therapeutic treatment to modulate the process of cell death after spinal cord trauma. This is the main line of the group currently, with studies focused on miR-138-5p and miR-199-5p and its effects on apoptosis and autophagy and on miR-135a-5p and the excitotoxicity mediated by the purinergic system.

 

2) development and validation of safe, effective and transferable tools to the clinical practice that allow the controlled administration of microRNAs for the treatment of spinal cord injury. For this, we have established collaborations with experts in nucleic acid chemistry of the Departamento de Nanotecnología Química y Biomolecular del Instituto de Química Avanzada de Cataluña (IQAC, CSIC) and experts in the synthesis, characterization and functionalization of polymeric biomaterials of the Grupo de Funcionalización de Polímeros del Instituto de Ciencia y Tecnología de Polímeros (ICTP, CSIC).

 

3) the development of computer support tools that allow to acquire, analyze and share information in experiments in spinal cord injury. This line is carried out in collaboration with the Institute Instituto de Informática de Albacete (I3A) and has begun with the development of a mobile / tablet app capable of recording and storing motor behavior information in mice;

 

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

 

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

 

6) modulation of central fatigue after spinal cord injury and other pathologies of the nervous system. This line, which is developed in collaboration with the FENNSI group of the Hospital Nacional de Paraplejicos, focuses on the evaluation of the drug Rimonabant, an inverse agonist / antagonist of the CB1 cannabinoid receptor, in animal models of spinal cord injury;

 

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

 

8) the characterization of programmed cell death processes (non-apoptotic) after spinal cord injury.

 

The laboratory uses a wide spectrum of molecular, histological, behavioral, and even bioinformatics techniques that allow the integral study of the processes involved in spinal cord injury and its treatments.

 

 

 

Relevant publications

 

- Pita-Thomas W, Fernández-Martos C, Yunta M, Martínez Maza R, Navarro-Ruiz R, López-Rodríguez MJ, Reigada D, Nieto-Sampedro M, Nieto-Díaz M. 2010. Gene expression of axon growth promoting factors in the deer antler. PLOS ONE 5 (12): e15706.

 

- Pita-Thomas, W, Maza RM, Nieto-Sampedro M, Nieto-Diaz M. 2010. Factors promoting neurite outgrowth during deer antler regeneration. J. Neuroscience Research 88 (14): 3034-3047.

 

- Nieto-Díaz, 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. Deer antler innervation and regeneration. 2012. Frontiers in Bioscience 17, 1389-1401.

 

- Yunta, M.; Nieto-Díaz, M.; Esteban, FJ.; Caballero-López, M.; Navarro-Ruiz, R.; Reigada, D.; Pita-Tomas, DW.; Águila, A.; Muñoz Galdeano, T. y Maza RM. Spinal cord injury induces general repression of microRNAs. 2012. PLoSOne 7(4): E35434.

 

- 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. Front Cell Neurosci. 8:53.

 

- 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.

 

- 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 Signal, 13(1):75-87.

 

- Pita-Thomas, Wolfgang; Barroso-García, Gemma; Moral, Veronica; Hackett, Amber R; Cavalli, Valeria; Nieto-Diaz, Manuel. 2016. Identification of axon growth promoters in the secretome of the deer antler velvet. Neuroscience340,333-344.

 

- 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 Mol Cell Res. 1864(7):1335-1348.

 

- 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

 

-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.Front Cell Neurosci. 12;12:164.

 

-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.J Neurochem. 151(1):116-130.

 

- 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.

 

- Klionski Det al. In press. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy.

 

 

 

Team

 

 

Rodrigo Martínez Maza: Principal Investigator; PhD in Biology

 

Manuel Nieto Díaz: Principal Investigator; PhD in Biology

 

David Reigada Prado: Researcher; PhD in Biology

 

Teresa Muñoz de Galdeano: Researcher; PhD in Pharmacology

 

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

 

Altea Soto Neira: Technician. Biology Degree.

 

 

 

Current projects

 

- MicroRNAs as a therapeutic strategy for trauma to the central nervous system: evaluation of the neuroprotective effect of miR-138 in the treatment of spinal cord injury. Funded by the Tatiana Pérez de Guzmán el Bueno Foundation (2017-2019). IPs: Teresa Muñoz de Galdeano and Rodrigo M. Maza.

 

- Use of Rimonabant as a treatment of central fatigue in spinal cord injury: rat trials. SAMOS Medical Enterprise SLU (2018-2019). IP: Manuel Nieto Díaz.

 

-Development and validation of new intelligent RNA administration systems in the injured spinal cord: application in a neuroprotective therapy based on miR-138. Ministry of Education, Community Board of Castilla La Mancha (2018-2020). IPs: Teresa Muñoz de Galdeano and Rodrigo M. Maza.

 

- Effects of a CB1 antagonist / inverse agonist (Rimonabant) on walking abilities and endurance in incomplete traumatic Spinal Cord Injury: a proof of principle study. IRP: International Foundation for Research in Paraplegia (2019-2021). IPs: Antonio Oliviero and Manuel Nieto-Díaz.