Felipe Court

Full Professor and Director of the CIB


Estudió biología en Chile trabajando en el laboratorio del Dr. Jaime Álvarez en síntesis local de proteínas en el axón. Luego obtuvoe un MSc y PhD en la Universidad de Edimburgo trabajando con los Dres. Richard Ribchester y Peter Brophy en enfermedades desmielinizantes del sistema nervioso periférico. Con una beca postdoctoral EMBO trabajó en el laboratorio de la Dra. Laura Feltri en Milán, Italia.Su investigación está enfocada en el estudio de la relación entre células gliales y neuronas en distintos procesos biológicos, incluyendo degeneración y regeneración axonal y transferencia intercelular de moléculas. Su laboratorio ha descrito nuevos mecanismos asociados a la degeneración axonal y demostrado que procesos locales en axones pueden ser regulados por la transferencia de RNA desde la célula glial al axón. Actualmente, esta además explorando mecanismos degenerativos en condiciones neurodegenerativas asociadas al envejecimiento como también cambios sistémicos que puedan gatillar eventos degenerativos que conllevan a pérdida funcional.


Felipe Court

PUBLICATIONS

Arrázola M.S. , Court F.A. 2019. Compartmentalized necroptosis activation in excitotoxicityinduced axonal degeneration: a novel mechanism implicated in neurodegenerative disease pathology. Neural Regen Res. 2019 Aug;14(8):1385-1386. doi: 10.4103/1673-5374.253520.

Catenaccio, A., and F.A. Court. 2018. Teased fiber preparation of myelinated nerve fibers from peripheral nerves for vital dye staining and immunofluorescence analysis. In Methods in Molecular Biology. 329–337.

Poitelon, Y., V. Matafora, N. Silvestri, D. Zambroni, C. McGarry, N. Serghany, T. Rush, D. Vizzuso, F.A. Court, A. Bachi, L. Wrabetz, and M.L. Feltri. 2018. A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies. J. Neurochem. 145:245–257. doi:10.1111/jnc.14295.

De Gregorio, C., P. Díaz, R. López-Leal, P. Manque, and F.A. Court. 2018. Purification of exosomes from primary Schwann cells, RNA extraction, and next-generation sequencing of exosomal RNAs. 1739. 299-315 pp.

Urra, H., D.R. Henriquez, J. Cánovas, D. Villarroel-Campos, A. Carreras-Sureda, E. Pulgar, E. Molina, Y.M. Hazari, C.M. Limia, S. Alvarez-Rojas, R. Figueroa, R.L. Vidal, D.A. Rodriguez, C.A. Rivera, F.A. Court, A. Couve, L. Qi, E. Chevet, R. Akai, T. Iwawaki, M.L. Concha, Á. Glavic, C. Gonzalez-Billault, and C. Hetz. 2018. IRE1α governs cytoskeleton remodelling and cell migration through a direct interaction with filamin A. Nat. Cell Biol. 20:942–953. doi:10.1038/s41556-018-0141-0.

López-Leal, R., P. Diaz, and F.A. Court. 2018. In Vitro Analysis of the Role of Schwann Cells on Axonal Degeneration and Regeneration Using Sensory Neurons from Dorsal Root Ganglia. 1739. 255-267 pp.

Müller, M., U. Ahumada-Castro, M. Sanhueza, C. Gonzalez-Billault, F.A. Court, and C. Cárdenas. 2018. Mitochondria and calcium regulation as basis of neurodegeneration associated with aging. Front. Neurosci. 12. doi:10.3389/fnins.2018.00470.

Gonzalez D., Rebolledo D .L., Correa LM., Court F.A., Cerpa W., Lipson K. E., van Zundert B., Brandan E. 2018. The inhibition of CTGF/CCN2 activity improves muscle and locomotor function in a murine ALS model. Hum Mol Genet. 2018 Aug 15;27(16):2913-2926. doi: 10.1093/hmg/ddy204.

Salvadores, N., M. Sanhueza, P. Manque, and F.A. Court. 2017. Axonal degeneration during aging and its functional role in neurodegenerative disorders. Front. Neurosci. 11. doi:10.3389/fnins.2017.00451.

Catenaccio, A., M. Llavero Hurtado, P. Diaz, D.J. Lamont, T.M. Wishart, and F.A. Court. 2017. Molecular analysis of axonal-intrinsic and glial-associated co-regulation of axon degeneration. Cell Death Dis. 8:e3166. doi:10.1038/cddis.2017.489.

Bargsted, L., D.B. Medinas, F. Martínez Traub, P. Rozas, N. Muñoz, M. Nassif, C. Jerez, A. Catenaccio, F.A. Court, C. Hetz, and S. Matus. 2017. Disulfide cross-linked multimers of TDP-43 and spinal motoneuron loss in a TDP-43A315TALS/FTD mouse model. Sci. Rep. 7. doi:10.1038/s41598-017-14399-5.

Martin, C., L. Leyton, M. Hott, Y. Arancibia, C. Spichiger, M.A. McNiven, F.A. Court, M.I. Concha, P. V. Burgos, and C. Otth. 2017. Herpes Simplex Virus Type 1 Neuronal Infection Perturbs Golgi Apparatus Integrity through Activation of Src Tyrosine Kinase and Dyn-2 GTPase. Front. Cell. Infect. Microbiol. 7. doi:10.3389/fcimb.2017.00371.

Macanas-Pirard, P., R. Broekhuizen, A. González, C. Oyanadel, D. Ernst, P. García, V.P. Montecinos, F. Court, M. Ocqueteau, P. Ramirez, and B. Nervi. 2017. Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome. Oncotarget. 8:23073–23086. doi:10.18632/oncotarget.14981.

Martin, C., L. Leyton, M. Hott, Y. Arancibia, C. Spichiger, M.A. McNiven, F.A. Court, M.I. Concha, P. V. Burgos, and C. Otth. 2017. Herpes Simplex Virus Type 1 Neuronal Infection Perturbs Golgi Apparatus Integrity through Activation of Src Tyrosine Kinase and Dyn-2 GTPase. Front. Cell. Infect. Microbiol. 7. doi:10.3389/fcimb.2017.00371.

Moreno, I., Edwards, G., Salvadores, N., Shahnawaz, M., Diaz-Espinoza, R., Soto, C. 2016. Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding. Molecular psychiatry

González, C., J. Cánovas, J. Fresno, E. Couve, F.A. Court, and A. Couve. 2016. Axons provide the secretory machinery for trafficking of voltage-gated sodium channels in peripheral nerve.Proc. Natl. Acad. Sci. 113:1823–1828. doi:10.1073/pnas.1514943113.

Bodaleo, F.J., C. Montenegro-Venegas, D.R. Henríquez, F.A. Court, and C. Gonzalez-Billault. 2016. Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology. Sci. Rep. 6. doi:10.1038/srep30069.

López-Leal, R., J. Alvarez, and F.A. Court. 2016. Origin of axonal proteins: Is the axon-schwann cell unit a functional syncytium? Cytoskeleton. 73:629–639. doi:10.1002/cm.21319.

Lopez-Leal, R., and F.A. Court. 2016. Schwann Cell Exosomes Mediate Neuron–Glia Communication and Enhance Axonal Regeneration. Cell. Mol. Neurobiol. 36:429–436. doi:10.1007/s10571-015-0314-3.

Valenzuela, V., M. Oñate, C. Hetz, and F.A. Court. 2016. Injury to the nervous system: A look into the ER. Brain Res. 1648:617–625. doi:10.1016/j.brainres.2016.04.053.

Court, F.A., and J. Alvarez. 2016. Schwann cell and axon: An interlaced unit—From action potential to phenotype expression. Adv. Exp. Med. Biol. 949:183–201. doi:10.1007/978-3-319-40764-7_9.

Oñate, M., A. Catenaccio, G. Martínez, D. Armentano, G. Parsons, B. Kerr, C. Hetz, and F.A. Court. 2016. Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury. Sci. Rep. 6. doi:10.1038/srep21709.

Oñate, M., F.A. Court, and C. Hetz. 2016. Bursting the unfolded protein response accelerates axonal regeneration. Neural Regen. Res. 11:892–893. doi:10.4103/1673-5374.184453.

Calvo, M., N. Richards, A.B. Schmid, A. Barroso, L. Zhu, D. Ivulic, N. Zhu, P. Anwandter, M.A. Bhat, F.A. Court, S.B. McMahon, and D.L.H. Bennett. 2016. Altered potassium channel distribution and composition in myelinated axons suppresses hyperexcitability following injury. Elife. 5. doi:10.7554/eLife.12661.

Oñate, M., A. Catenaccio, G. Martínez, D. Armentano, G. Parsons, B. Kerr, C. Hetz, and F.A. Court. 2016. Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury. Sci. Rep. 6. doi:10.1038/srep21709.

Pasten, C., J. Cerda, I. Jausoro, F.A. Court, A. Cáceres, and M.P. Marzolo. 2015. ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1. Mol. Cell. Neurosci. 69:1–11. doi:10.1016/j.mcn.2015.09.004.

Holland, P.R., J.L. Searcy, N. Salvadores, G. Scullion, G. Chen, G. Lawson, F. Scott, M.E. Bastin, M. Ihara, R. Kalaria, E.R. Wood, C. Smith, J.M. Wardlaw, and K. Horsburgh. 2015. Gliovascular disruption and cognitive deficits in a mouse model with features of small vessel disease. J. Cereb. Blood Flow Metab. 35:1005–1014. doi:10.1038/jcbfm.2015.12.

Pasten, C., J. Cerda, I. Jausoro, F.A. Court, A. Cáceres, and M.P. Marzolo. 2015. ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1. Mol. Cell. Neurosci. 69:1–11. doi:10.1016/j.mcn.2015.09.004.

Castillo, V., M. Oñate, U. Woehlbier, P. Rozas, C. Andreu, D. Medinas, P. Valdés, F. Osorio, G. Mercado, R.L. Vidal, B. Kerr, F.A. Court, and C. Hetz. 2015. Functional role of the disulfide isomerase ERp57 in axonal regeneration. PLoS One. 10. doi:10.1371/journal.pone.0136620.

Lener, T., M. Gimona, L. Aigner, V. Börger, E. Buzas, G. Camussi, N. Chaput, D. Chatterjee, F.A. Court, H.A. del Portillo, L. O’Driscoll, S. Fais, J.M. Falcon-Perez, U. Felderhoff-Mueser, L. Fraile, Y.S. Gho, A. Görgens, R.C. Gupta, A. Hendrix, D.M. Hermann, A.F. Hill, F. Hochberg, P.A. Horn, D. de Kleijn, L. Kordelas, B.W. Kramer, E.M. Krämer-Albers, S. Laner-Plamberger, S. Laitinen, T. Leonardi, M.J. Lorenowicz, S.K. Lim, J. Lötvall, C.A. Maguire, A. Marcilla, I. Nazarenko, T. Ochiya, T. Patel, S. Pedersen, G. Pocsfalvi, S. Pluchino, P. Quesenberry, I.G. Reischl, F.J. Rivera, R. Sanzenbacher, K. Schallmoser, I. Slaper-Cortenbach, D. Strunk, T. Tonn, P. Vader, B.W.M. van Balkom, M. Wauben, S. El Andaloussi, C. Théry, E. Rohde, and B. Giebel. 2015. Applying extracellular vesicles based therapeutics in clinical trials - An ISEV position paper. J. Extracell. Vesicles. 4. doi:10.3402/jev.v4.30087.

Rojas, F., D. Gonzalez, N. Cortes, E. Ampuero, D.E. Hernández, E. Fritz, S. Abarzua, A. Martinez, A.A. Elorza, A. Alvarez, F. Court, and B. van Zundert. 2015. Reactive oxygen species trigger motoneuron death in non-cell-autonomous models of ALS through activation of c-Abl signaling. Front. Cell. Neurosci. 09. doi:10.3389/fncel.2015.00203.

Castillo, V., M. Oñate, U. Woehlbier, P. Rozas, C. Andreu, D. Medinas, P. Valdés, F. Osorio, G. Mercado, R.L. Vidal, B. Kerr, F.A. Court, and C. Hetz. 2015. Erratum: Functional role of the disulfide isomerse ERp57 in axonal regeneration (PLoS ONE (2015) 10:9 (e0136620) DOI:10.1371/journal.pone.0136620). PLoS One. 10. doi:10.1371/journal.pone.0140200.

Villegas, R., N.W. Martinez, J. Lillo, P. Pihan, D. Hernandez, J.L. Twiss, and F.A. Court. 2014. Calcium Release from Intra-Axonal Endoplasmic Reticulum Leads to Axon Degeneration through Mitochondrial Dysfunction. J. Neurosci. 34:7179–7189. doi:10.1523/JNEUROSCI.4784-13.2014.

Valdes, P., G. Mercado, R.L. Vidal, C. Molina, G. Parsons, F.A. Court, A. Martinez, D. Galleguillos, D. Armentano, B.L. Schneider, and C. Hetz. 2014. Control of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1. Proc. Natl. Acad. Sci. 111:6804–6809. doi:10.1073/pnas.1321845111.

Escudero, C.A., O.M. Lazo, C. Galleguillos, J.I. Parraguez, M.A. Lopez-Verrilli, C. Cabeza, L. Leon, U. Saeed, C. Retamal, A. Gonzalez, M.-P. Marzolo, B.D. Carter, F.A. Court, and F.C. Bronfman. 2014. The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release. J. Cell Sci. 127:1966–1979. doi:10.1242/jcs.141754.

Rajendran, L., J. Bali, M.M. Barr, F.A. Court, E.-M. Kramer-Albers, F. Picou, G. Raposo, K.E. van der Vos, G. van Niel, J. Wang, and X.O. Breakefield. 2014. Emerging Roles of Extracellular Vesicles in the Nervous System. J. Neurosci. 34:15482–15489. doi:10.1523/JNEUROSCI.3258-14.2014.

Collyer, E., A. Catenaccio, D. Lemaitre, P. Diaz, V. Valenzuela, F. Bronfman, and F.A. Court. 2014. Sprouting of axonal collaterals after spinal cord injury is prevented by delayed axonal degeneration. Exp. Neurol. 261:451–461. doi:10.1016/j.expneurol.2014.07.014.

Lopez-Verrilli, M.A., and F.A. Court. 2013. Exosomes: Mediators of communication in eukaryotes. Biol. Res. 46:5–11. doi:10.4067/S0716-97602013000100001.

Castillo, K., V. Valenzuela, S. Matus, M. Nassif, M. Oñate, Y. Fuentealba, G. Encina, T. Irrazabal, G. Parsons, F.A. Court, B.L. Schneider, D. Armentano, and C. Hetz. 2013. Measurement of autophagy flux in the nervous system in vivo. Cell Death Dis. 4. doi:10.1038/cddis.2013.421.

Lopez-Verrilli, M.A., F. Picou, and F.A. Court. 2013. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia. 61:1795–1806. doi:10.1002/glia.22558.

Castillo, K., M. Nassif, V. Valenzuela, F. Rojas, S. Matus, G. Mercado, F.A. Court, B. Van Zundert, and C. Hetz. 2013. Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons. Autophagy. 9:1308–1320. doi:10.4161/auto.25188.

Cortés, C., E. Eugenin, E. Aliaga, L.J. Carreño, S.M. Bueno, P.A. Gonzalez, S. Gayol, D. Naranjo, V. Noches, M.P. Marassi, D. Rosenthal, C. Jadue, P. Ibarra, C. Keitel, N. Wohllk, F. Court, A.M. Kalergis, and C.A. Riedel. 2012. Hypothyroidism in the Adult Rat Causes Incremental Changes in Brain-Derived Neurotrophic Factor, Neuronal and Astrocyte Apoptosis, Gliosis, and Deterioration of Postsynaptic Density. Thyroid. 22:951–963. doi:10.1089/thy.2010.0400.

Valenzuela, V., E. Collyer, D. Armentano, G.B. Parsons, F.A. Court, and C. Hetz. 2012. Activation of the unfolded protein response enhances motor recovery after spinal cord injury. Cell Death Dis. 3. doi:10.1038/cddis.2012.8.

Calixto, A., J.S. Jara, and F.A. Court. 2012. Diapause Formation and Downregulation of Insulin-Like Signaling via DAF-16/FOXO Delays Axonal Degeneration and Neuronal Loss. PLoS Genet. 8. doi:10.1371/journal.pgen.1003141.

Zamorano, S., D. Rojas-Rivera, F. Lisbona, V. Parra, F.A. Court, R. Villegas, E.H. Cheng, S.J. Korsmeyer, S. Lavandero, and C. Hetz. 2012. A BAX/BAK and cyclophilin D-independent intrinsic apoptosis pathway. PLoS One. 7. doi:10.1371/journal.pone.0037782.

Vidal, R.L., A. Figueroa, F.A. Court, P. Thielen, C. Molina, C. Wirth, B. Caballero, R. Kiffin, J. Segura-Aguilar, A.M. Cuervo, L.H. Glimcher, and C. Hetz. 2012. Targeting the UPR transcription factor XBP1 protects against Huntington’s disease through the regulation of FoxO1 and autophagy. Hum. Mol. Genet. 21:2245–2262. doi:10.1093/hmg/dds040.

Lopez-Verrilli, M.A., and F.A. Court. 2012. Transfer of vesicles from Schwann cells to axons: A novel mechanism of communication in the peripheral nervous system. Front. Physiol. 3 JUN. doi:10.3389/fphys.2012.00205.

Court F.A., Coleman MP. 2012. Mitochondria as a central sensor for axonal degenerative stimuli. Trends Neurosci. 35(6):364-72.

Court, F.A., and J. Álvarez. 2011. Slow axoplasmic transport under scrutiny. Biol. Res. 44:311–321. doi:10.4067/S0716-97602011000400001.

Castillo, K., D. Rojas-Rivera, F. Lisbona, B.N. Caballero, M. Nassif, F.A. Court, S. Schuck, C. Ibar, P. Walter, J. Sierralta, A. Glavic, and C. Hetz. 2011. BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response. EMBO J. 30:4465–4478. doi:10.1038/emboj.2011.318.

Court, F.A., D. Zambroni, E. Pavoni, C. Colombelli, C. Baragli, G. Figlia, L. Sorokin, W. Ching, J.L. Salzer, L. Wrabetz, and M.L. Feltri. 2011. MMP2-9 Cleavage of Dystroglycan Alters the Size and Molecular Composition of Schwann Cell Domains. J. Neurosci. 31:12208–12217. doi:10.1523/JNEUROSCI.0141-11.2011.

Court, F.A., R. Midha, B.A. Cisterna, J. Grochmal, A. Shakhbazau, W.T. Hendriks, and J. Van Minnen. 2011. Morphological evidence for a transport of ribosomes from Schwann cells to regenerating axons. Glia. 59:1529–1539. doi:10.1002/glia.21196.

Barrientos, S.A., N.W. Martinez, S. Yoo, J.S. Jara, S. Zamorano, C. Hetz, J.L. Twiss, J. Alvarez, and F.A. Court. 2011. Axonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore. J. Neurosci. 31:966–978. doi:10.1523/JNEUROSCI.4065-10.2011.

Castillo, K., D. Rojas-Rivera, F. Lisbona, B.N. Caballero, M. Nassif, F.A. Court, S. Schuck, C. Ibar, P. Walter, J. Sierralta, A. Glavic, and C. Hetz. 2011. BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response. EMBO J. 30:4465–4478. doi:10.1038/emboj.2011.318.

Rio, R. Del, C. Muñoz, P. Arias, F.A. Court, E.A. Moya, and R. Iturriaga. 2011. Chronic intermittent hypoxia-induced vascular enlargement and VEGF upregulation in the rat carotid body is not prevented by antioxidant treatment. Am. J. Physiol. - Lung Cell. Mol. Physiol. 301:L702–L711. doi:10.1152/ajplung.00128.2011.

Hetz, C., P. Thielen, S. Matus, M. Nassif, F. Court, R. Kiffin, G. Martinez, A.M. Cuervo, R.H. Brown, and L.H. Glimcher. 2009. XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy. Genes Dev. 23:2294–2306. doi:10.1101/gad.1830709.

Court, F.A., J.E. Hewitt, K. Davies, B.L. Patton, A. Uncini, L. Wrabetz, and M.L. Feltri. 2009. A Laminin-2, Dystroglycan, Utrophin Axis Is Required for Compartmentalization and Elongation of Myelin Segments. J. Neurosci. 29:3908–3919. doi:10.1523/JNEUROSCI.5672-08.2009.

Nodari, A., S.C. Previtali, G. Dati, S. Occhi, F.A. Court, C. Colombelli, D. Zambroni, G. Dina, U. Del Carro, K.P. Campbell, A. Quattrini, L. Wrabetz, and M.L. Feltri. 2008. 6 4 Integrin and Dystroglycan Cooperate to Stabilize the Myelin Sheath. J. Neurosci. 28:6714–6719. doi:10.1523/JNEUROSCI.0326-08.2008.

Court, F.A., P.J. Brophy, and R.R. Ribchester. 2008. Remodeling of motor nerve terminals in demyelinating axons of periaxin-null mice. Glia. 56:471–479. doi:10.1002/glia.20620.

Court, F.A., T.H. Gillingwater, S. Melrose, D.L. Sherman, K.N. Greenshields, A.J. Morton, J.B. Harris, H.J. Willison, and R.R. Ribchester. 2008. Identity, developmental restriction and reactivity of extralaminar cells capping mammalian neuromuscular junctions. J. Cell Sci. 121:3901–3911. doi:10.1242/jcs.031047.

Court, F.A., W.T.J. Hendriks, H.D. MacGillavry, J. Alvarez, and J. van Minnen. 2008. Schwann Cell to Axon Transfer of Ribosomes: Toward a Novel Understanding of the Role of Glia in the Nervous System. J. Neurosci. 28:11024–11029. doi:10.1523/JNEUROSCI.2429-08.2008.

Villablanca, E.J., A. Pistocchi, F. a Court, F. Cotelli, C. Bordignon, M.L. Allende, C. Traversari, and V. Russo. 2007. Abrogation of prostaglandin E2/EP4 signaling impairs the development of rag1+ lymphoid precursors in the thymus of zebrafish embryos. J. Immunol. 179:357–64. doi:10.4049/jimmunol.179.1.357.

Nodari, A., D. Zambroni, A. Quattrini, F.A. Court, A. D’Urso, A. Recchia, V.L.J. Tybulewicz, L. Wrabetz, and M.L. Feltri. 2007. β1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination. J. Cell Biol. 177:1063–1075. doi:10.1083/jcb.200610014.

Court, F.A., L. Wrabetz, and M.L. Feltri. 2006. Basal lamina: Schwann cells wrap to the rhythm of space-time. Curr. Opin. Neurobiol. 16:501–507. doi:10.1016/j.conb.2006.08.005.

Court, F.A., and J. Álvarez. 2005. Local regulation of the axonal phenotype, a case of merotrophism. Biol. Res. 38:365–374. doi:10.4067/S0716-97602005000400009.

Sherman, D.L., S. Tait, S. Melrose, R. Johnson, B. Zonta, F.A. Court, W.B. Macklin, S. Meek, A.J.H. Smith, D.F. Cottrell, and P.J. Brophy. 2005. Neurofascins are required to establish axonal domains for saltatory conduction. Neuron. 48:737–742. doi:10.1016/j.neuron.2005.10.019.

Ribchester, R.R., D. Thomson, N.I. Wood, T. Hinks, T.H. Gillingwater, T.M. Wishart, F.A. Court, and A.J. Morton. 2004. Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington’s disease mutation. Eur. J. Neurosci. 20:3092–3114. doi:10.1111/j.1460-9568.2004.03783.x.

Court, F.A., D.L. Sherman, T. Pratt, E.M. Garry, R.R. Ribchester, D.F. Cottrell, S.M. Fleetwood-Walker, and P.J. Brophy. 2004. Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves. Nature. 431:191–195. doi:10.1038/nature02841.

Ninkina, N., K. Papachroni, D.C. Robertson, O. Schmidt, L. Delaney, F. O’Neill, F. Court, A. Rosenthal, S.M. Fleetwood-Walker, A.M. Davies, and V.L. Buchman. 2003. Neurons Expressing the Highest Levels of g-Synuclein Are Unaffected by Targeted Inactivation of the Gene. Mol. Cell. Biol. 23:8233–8245. doi:10.1128/MCB.23.22.8233-8245.2003.

Mack, T.G.A., M. Reiner, B. Beirowski, W. Mi, M. Emanuelli, D. Wagner, D. Thomson, T. Gillingwater, F. Court, L. Conforti, F.S. Fernando, A. Tarlton, C. Andressen, K. Addicks, G. Magni, R.R. Ribchester, V.H. Perry, and M.P. Coleman. 2001. Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat. Neurosci. 4:1199–1206. doi:10.1038/nn770.

Court, F., and J. Alvarez. 2000. Nerve regeneration in Wld(s) mice is normalized by actinomycin D. Brain Res. 867:1–8. doi:10.1016/S0006-8993(00)02140-5.

RESEARCH LINES

1. Axonal degeneration as a target for neuroprotection

1. Axonal degeneration as a target for neuroprotection

Axonal degeneration is an active mechanism involved in a variety of neurodegenerative conditions triggered by mechanical, metabolic, infectious, toxic, hereditary and inflammatory stimuli. Importantly, axonal degeneration and synapse loss have been proposed as an early event and major contributor to neuronal death in several neurodegenerative conditions, including Parkinson, Alzheimer, Huntington, demyelinating, motoneuron, and prion diseases. Axon degeneration can cause permanent loss of function, so it represents a focus for neuroprotective strategies. We are investigating the impact of axonal degeneration in physiological and pathological conditions as well as the molecular mechanism involved in this degenerative process.

2. Vesicular transfer of genetic material in the nervous system

2. Vesicular transfer of genetic material in the nervous system

Glial cells and neurons have multiple mechanisms for bidirectional comunication. We have shown that transcellular transfer of macromolecules take place from glia to axons after injury and during axonal regeneration. We are currently studying the communication and macromolecular transfer mechanisms between glial cells and axons mediated by secreted vesicles. Our ultimate goal is to define the role of vesicular transfer between glia and neurons in the regulation of different axonal processes, including neuronal maintenance and axonal regeneration in the peripheral and central nervous system.

3. Mechanisms for axonal regeneration and collateral sprouting

3. Mechanisms for axonal regeneration and collateral sprouting

Damage to the nervous system as well as degeneration of axonal tracts due to neurodegenerative conditions results in functional impairment. Currently there are no effective therapies to enhance regenerative processes and functional recovery in the nervous system. We are trying to unravel the mechanisms involved in axonal regeneration and collateral sprouting after peripheral and central injuries using different approaches, including transcriptomic analysis in newly developed models of collateral sprouting as well as gene therapy approaches.

4. Activation of degenerative processes during ageing

4. Activation of degenerative processes during ageing

As part of the Geroscience FONDAP Center we are investigating modification of degenerative processes due to ageing, which is the principal risk factor for developing chronic diseases, including neurodegenerative conditions. Currently we are studying the impact of age associated inflammation in axonal degeneration and its relationship to lost of cognitive function, as well a

PROJECTS

Name: FONDAP Geroscience

Title: Geroscience, mental health and metabolism.

Funding Institution: CONICYT 15150012

Responsible Researcher: Felipe Court

Date of execution: 2015-2020

Name: International / The Michael J. Fox Foundation for Parkinson's Research (MJFF)

Title: Focus necroptosis to inhibit early axonal degeneration in Parkinson's disease

Funding Institution: The Michael J. Fox Foundation for Parkinson's Research (MJFF)

Responsible Researcher: Felipe Court

Date of execution: 2019-2021

Name: REDES

Title: A multi-model collaborative network to study the development and function of the nervous system in health and disease.

Institution that finances: CONICYT

Responsible Researcher: Felipe Court

Date of execution: 2018-2020

Name: ECOS

Title: Investigation of the role of caveola-dependent mechanosension in the interaction of glial cells with neurons

Institution that finances: CONICYT

Responsible Researcher: Felipe Court

Date of execution: 2017-2020

TEAM

Alejandra Catenaccio

Research Assistant

Bachelor in Molecular Biology from the National University of San Luis, Argentina. Working in a FONDEF project related to spinal cord injury and also investigating the role glial cells in axonal degeneration at the peripheral nervous system.

José Ángel Landa

Lab Manager

Business Manager from Universidad Privada del Estado de Morelos, México

Cristian Saquel

Research Assistant

M.Sc. in biotechnology from the Andrés Bello University. Currently working on to the transfer of miRNA from Schwann cells to neurons mediated by exosomes and their impact on axonal regeneration.

Romina Catalán

Research Assistant

Biochemist from University of Santiago of Chile. Working on to the Transfer of RNA from Schwann cell to neurons mediated by exosomes and their impact upon axonal regeneration and neuronal survival.

Gabriela Caceres

Research Assistant

Medical Technologist majored in Morpho-Physiopathology and Cytodiagnosis in Universidad Mayor and candidate to the Master Program in Medical and Biological Sciences, mention in Genetics, of the University of Chile. I’m currently working on processing tissues and carrying out histological techniques for different researches conducted in the laboratory.

Alejandra Palma

Research Assistant

Biochemist from Universidad San Sebastián and MSc biochemistry and bioinformatics from the University of Concepción. Working in MJ-FOX project about targeting necroptosis to inhibit axonal degeneration in Parkinson disease.

Natalia Salvadores

Postdoctoral fellow

Biochemist, Ph.D. in Biological Sciences from the University of Edinburgh. Studying mechanisms of axonal degeneration in age-related neurodegenerative diseases using in vitro and in vivo model.

Macarena Arrazola

Postdoctoral fellow

PhD in Biological Sciences from the Catholic University of Chile. Studying the contribution of chronic inflammation in neurodegeneration along aging and the role of necroptosis in the vulnerability of different neuronal populations of the aged brain.

Cristian Geronimo

Postdoctoral fellow

PhD in Biochemical Sciences from Universidad Nacional Autónoma de México (UNAM). Studying the role of senescent Schwann cells on neuronal intrinsic growth mechanisms during axonal regeneration.

Sergio Benitez

Postdoctoral fellow

Geneticist from National University of Misiones and PhD in Biological Sciences from the National University of Cordoba, Argentina. I’m currently working on the characterization of the aging impact on the microbiota-gut-brain axis and its implication in neurodegenerative diseases.

Andrés Fuentes

PhD Student

Biotechnologist and PhD in Integrative Genomics from the Mayor University, Chile. Working in the age-dependent molecular and cellular mechanisms of glial-axon interaction mediating regeneration after PNS injury.

Francisco Muñoz

PhD Student

Biotechnology Student, Universidad Mayor. PhD student in Neurobiology at Center for Integrative Biology (CIB). Universidad Mayor. Working on axonal degeneration using Drosophila as a model.

NETWORK

National

Claudio Hetz, Facultad de Medicina, Universidad de Chile.

Patricio Manque, Centro de Genómica y Bioinformática, Universidad Mayor.

Felipe Barros, CECS, Valdivia, Chile.

International

Gregorio Iraola, Instituto Pasteur, Uruguay.

Patricia Setton, Facultad Farmacia y Bioquímica, UBA, Argentina.

Thomas Wishart, Roslin Institute, Edinburgh University, UK.

Frederic Charron, Institut de Recherches Cliniques de Montreal, Canadá.

Avraham Yaron, Weizmann Institute, Israel.