Molecular Neuroprotection

Grupo de Neuroprotección Molecular

Molecular Neuroprotection

 

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

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

 

Specialization (UNESCO code): 320101, 320711, 2415

 

Our group has two main research objectives:

 

1) to characterize cellular and molecular mechanisms underlying neurodegenerative disorders, particularly  those typical of the spinal cord lesion,

 

 2) to develop and evaluate neuroprotective therapies that would counteract harmful effects produced by spinal injuries.

 

To address the first objective our work has been centered on characterizing the apoptotic processes induced by the spinal cord injury and the factors involved in their regulation. In the last years, we have expanded the scope of our studies to include two other forms of programmed cellular death, namelynecroptosis and autophagy.

 

To address the second objective, our initial studies were focused on testing the therapeutic potential of apoptosis inhibiting proteins (IAPs). However, incorporation of new staff has lead to new approachesand targets, such as:

  1. microRNAs, due to their role as global regulators of gene expression and cellular conditions,
  2. thepurinergic system , involved in the excitotoxic and apoptotic processes following trauma
  3. and ultimately, sphingosine-1-phosphate, a sphingolipid implicated in the regulation of processes such as cell death, regeneration and glial activity.

 

Our group is also developing a novel research line focused on deer antlers as a model of mammalian neural regeneration. In addition, we have ongoing collaborations with informatics expertsaiming to develop tools to analyse, store, and share data from experimental spinal cord injury studies.

 

In the laboratory we employ a broad range of molecular (e.g. proteomics and functional genomics), histological, cellular, behavioral and computational techniques that allow us an integrative approach to the processestaking place after spinal lesions and search for their treatments.

 

 

 

Selected publications

 

- Nieto-Diaz M,  Esteban FJ, Reigada D, Munoz-Galdeano T, Yunta M, Caballero-Loopez M, Navarro-Ruiz R, del Aguila A, Maza RM. MicroRNA dysregulation in spinal cord injury: causes, consequences, and therapeutics. Front Cell Neurosci. 2014; 8:53. doi:0.3389/fncel.2014.00053.

 

- Martinez-Maza C, Alberdi MT, Nieto-Diaz M, Prado JL. Life-History Traits of the Miocene Hipparionconcudense (Spain) Inferred from Bone Histological Structure. PLoS ONE. 2014; 9(8):e103708. doi: 10.1371/journal.pone.0103708.

 

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

 

- Martín-López E,  Alonso FR, Nieto-Diaz M, Nieto-Sampedro M. Chitosan, gelatin and poly-l-lysine polyelectrolyte-based scaffolds and films for neural tissue engineering. 2012. Journal of Biomaterials Science: Polymer Edition 23, 207–232.

 

- Nieto-Diaz, M.; Pita-Thomas DW. Munoz-Galdeano T, Martinez-Maza C, Navarro-Ruiz R, Reigada D, Yunta-Gonzalez M, Caballero-Lopez MJ, Nieto-Sampedro M, Martinez-Maza R. Deerantlerinnervation and regeneration. 2012. Frontiers in Bioscience 17, 1389-1401.

 

- Nieto-Diaz M, Esteban FJ, Reigada D, Muñoz-Galdeano T, Yunta M, Caballero-López M, Navarro-Ruiz R, Del Águila A, Maza RM.2014. MicroRNAdysregulation in spinalcordinjury: causes, consequences and therapeutics. Front CellNeurosci. 8:53.

 

- Reigada D, Nieto-Díaz M, Navarro-Ruiz R, Caballero-López MJ, Del Águila A, Muñoz-Galdeano T, Maza RM. 2015. Acuteadministration of ucf-101 amelioratesthe locomotor impairmentsinducedby a traumaticspinalcordinjury.  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. Diadenosinetetraphosphate (Ap4A) inhibits ATP-inducedexcitotoxicity: a neuroprotectivestrategyfortraumaticspinalcordinjurytreatment. Purinergic Signalling,1-13 (ePubahead of print).

 

- Pita-Thomas, Wolfgang; Barroso-García, Gemma; Moral, Veronica; Hackett, Amber R; Cavalli, Valeria; Nieto-Diaz, Manuel. 2016. Identification of axongrowthpromoters in thesecretome of thedeerantlervelvet. Neuroscience340,333-344.

 

 

 

Personnel

 

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 Pharmacology

 

María de los Ángeles del Águila Sánchez: PhD. Student; BSc. in Chemistry

 

 

 

Ongoing projects

 

- MicroRNAs and secondary cell death in spinal cord injury: new diagnostic and therapeutic tools.

PI: Rodrigo Maza. Funded by the Ministry of Economy and Competitiveness (Instituto de Salud Carlos III; 2013-2015)

 

- MicroRNAs as a therapeutic strategy for Central Nervous System trauma: evaluating the protective role of miR-138 in spinal cord injury

PI: Teresa Muñoz-Galdeano&Rodrigo Maza. Funded by Tatiana Perez de Guzman el Bueno Foundation (2017-2019)

 

 

 

 Research lines

 

- The neuroprotective action of apoptosis inhibiting proteins (IAPs) as a  therapeutic treatment against the secondary spinal damage following spinal cord injuries.

 

- Evaluation of microRNAs as potential therapeutic treatments for the spinal cord injury.Development of new therapeutic tools for modulating miRNA expression in vivo.

 

- Evaluating the therapeutic potential of diadenosinetetraphosphate as a treatment for secondary damage to the spinal cord.

 

- Characterization of non-apoptotic, programed cell death processes following the spinal cord injury.

 

- Sphingosine 1 phosphate as a therapeutic target for the spinal cord injury.

 

- Rapid axonal growth and regeneration in adult mammals: identifying neuroprotective and neuroregenerative mechanisms with a potential clinical application.

 

- New tools for recording, storing and sharing behavioural data from rodent models of spinal cord injury.