Vidal

Rene Vidal

Assistant Professor


RENE.VIDAL@UMAYOR.CL


The imbalance of Proteostasis has been described as one of the most relevant factors in the aging process and thus neurodegenerative diseases. The focus of our laboratory is to understand the molecular mechanisms involved in the neurodegeneration process and in the development of therapies, both pharmacological and genetic, which leading the reestablishment of neuronal Proteostasis. Specifically, we are studying new molecules using gene therapy strategies in preclinical models of Parkinson Disease and Huntington Disease.

Additionally, we are working with Chilean’s Parkinson and Huntington patients to study the neurodegenerative processes, through the analysis of blood samples. To understand the biochemical changes that are generated during the development of the disease, and to describe new biomarkers present exclusively in our population.

Finally, we belong to Center for Geroscience, Brain Health and Metabolism. This project will provide to us new tools to study neurodegenerative processes, both clinically and pre-clinically levels. Our aim is determining the cellular and molecular mechanisms associated to aging, and its impact in the development of neurodegenerative diseases.



Paulina Troncoso-Escudero, Alejandra Parra, Melissa Nassif, Rene L. Vidal (2018). Outside in: unraveling the role of neuroinflammation in the progression of Parkinson’s disease. Frontiers in Neurology. 9:860.doi:10.3389/ fneur.2018.00860.

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. doi:10.1038/s41556-018-0141-0.

Woehlbier, U., A. Colombo, M.J. Saaranen, V. Pérez, J. Ojeda, F.J. Bustos, C.I. Andreu, M. Torres, V. Valenzuela, D.B. Medinas, P. Rozas, R.L. Vidal, R. Lopez-Gonzalez, J. Salameh, S. Fernandez-Collemann, N. Muñoz, S. Matus, R. Armisen, A. Sagredo, K. Palma, T. Irrazabal, S. Almeida, P. Gonzalez-Perez, M. Campero, F.-B. Gao, P. Henny, B. Van Zundert, L.W. Ruddock, M.L. Concha, J.P. Henriquez, R.H. Brown, and C. Hetz. 2016. ALS-linked protein disulfide isomerase variants cause motor dysfunction. EMBO J. 35. doi:10.15252/embj.201592224.

Garcia-Huerta, P., P. Troncoso-Escudero, C. Jerez, C. Hetz, and R.L. Vidal. 2016. The intersection between growth factors, autophagy and ER stress: A new target to treat neurodegenerative diseases? Brain Res. 1649. doi:10.1016/j.brainres.2016.02.052.

Garcia-Huerta, P., L. Bargsted, A. Rivas, S. Matus, and R.L. Vidal. 2016. ER chaperones in neurodegenerative disease: Folding and beyond. Brain Res. 1648. doi:10.1016/j.brainres.2016.04.070.

Martínez, G., R.L. Vidal, P. Mardones, F.G. Serrano, A.O. Ardiles, C. Wirth, P. Valdés, P. Thielen, B.L. Schneider, B. Kerr, J.L. Valdés, A.G. Palacios, N.C. Inestrosa, L.H. Glimcher, and C. Hetz. 2016. Regulation of Memory Formation by the Transcription Factor XBP1. Cell Rep. 14. doi:10.1016/j.celrep.2016.01.028.

Bargsted, L., R.L. Vidal, C. Hetz, and S. Matus. 2015. Dual role of autophagy in neurodegenerative diseases: The case of amyotrophic lateral sclerosis.

Rivas, A., R.L. Vidal, and C. Hetz. 2015. Targeting the unfolded protein response for disease intervention. Expert Opin. Ther. Targets. 19. doi:10.1517/14728222.2015.1053869.

Mercado, G., V. Castillo, R. Vidal, and C. Hetz. 2015. ER proteostasis disturbances in Parkinson’s disease: Novel insights. Front. Aging Neurosci. 7. doi:10.3389/fnagi.2015.00039.

Vidal, R.L., S. Matus, L. Bargsted, and C. Hetz. 2014. Targeting autophagy in neurodegenerative diseases. Trends Pharmacol. Sci. 35. doi:10.1016/j.tips.2014.09.002.

Acuña, A.I., M. Esparza, C. Kramm, F.A. Beltrán, A.V. Parra, C. Cepeda, C.A. Toro, R.L. Vidal, C. Hetz, I.I. Concha, S. Brauchi, M.S. Levine, and M.A. Castro. 2013. A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice. Nat. Commun. 4. doi:10.1038/ncomms3917.

Cornejo, V.H., P. Pihán, R.L. Vidal, and C. Hetz. 2013. Role of the unfolded protein response in organ physiology: Lessons from mouse models. IUBMB Life. 65. doi:10.1002/iub.1224.

Vidal, R.L., and C. Hetz. 2013. Unspliced XBP1 controls autophagy through FoxO1. Cell Res. 23. doi:10.1038/cr.2013.9.

Zuleta, A., R.L. Vidal, D. Armentano, G. Parsons, and C. Hetz. 2012. AAV-mediated delivery of the transcription factor XBP1s into the striatum reduces mutant Huntingtin aggregation in a mouse model of Huntington’s disease. Biochem. Biophys. Res. Commun. 420. doi:10.1016/j.bbrc.2012.03.033.

Vidal, R.L., P. Fuentes, J.I. Valenzuela, C.P. Alvarado-Diaz, O.A. Ramírez, M. Kukuljan, and A. Couve. 2012. RNA interference of Marlin-1/Jakmip1 results in abnormal morphogenesis and migration of cortical pyramidal neurons. Mol. Cell. Neurosci. 51. doi:10.1016/j.mcn.2012.07.007.

Vidal, R.L., and C. Hetz. 2012. Crosstalk between the UPR and autophagy pathway contributes to handling cellular stress in neurodegenerative disease. Autophagy. 8. doi:10.4161/auto.20139.

Vidal, R., B. Caballero, A. Couve, and C. Hetz. 2011. Converging pathways in the occurrence of endoplasmic reticulum (er) stress in Huntington’s disease. Curr. Mol. Med. 11. doi:10.2174/156652411794474419.

Vidal, R.L., J.I. Valenzuela, R. Luján, and A. Couve. 2009. Cellular and subcellular localization of Marlin-1 in the brain. BMC Neurosci. 10. doi:10.1186/1471-2202-10-37.

Ramírez, O.A., R.L. Vidal, J.A. Tello, K.J. Vargas, S. Kindler, S. Härtel, and A. Couve. 2009. Dendritic assembly of heteromeric γ-aminobutyric acid type B receptor subunits in hippocampal neurons. J. Biol. Chem. 284. doi:10.1074/jbc.M900575200.

Vidal, R.L., A. Ramírez, M. Castro, I.I. Concha, and A. Couve. 2008. Marlin-1 is expressed in testis and associates to the cytoskeleton and GABAB receptors. J. Cell. Biochem. 103. doi:10.1002/jcb.21456.

Vidal, R.L., O.A. Ramírez, L. Sandoval, R. Koenig-Robert, S. Härtel, and A. Couve. 2007. Marlin-1 and conventional kinesin link GABA<inf>B</inf>receptors to the cytoskeleton and regulate receptor transport. Mol. Cell. Neurosci. 35. doi:10.1016/j.mcn.2007.04.008.

1.png#asset:841. Gene and Pharmacological therapy to treatment Parkinson and Huntington Disease
Our laboratory is focused on determining the therapeutic potential of specific drugs / genes that delay the progression of neurodegenerative diseases. These diseases occur by the loss of specific neuronal groups that are involved in the motor or cognitive symptoms observed in patients. One of the possible causes of this neuronal death is the imbalance of protein homeostasis (Proteostasis). In our laboratory, we investigate cellular pathways involved in reestablishing Proteostasis balance in the brain, using viral vectors (gene therapy) to manipulate the key components involved in protein quality control, trophic factors, autophagy and others. We also studied the impact of new drugs such as Rapalogs (analogs of rapamycin), which can modulate the autophagy pathway and improve the degradation of misfolded proteins that contribute to the neurodegenerative process in the Central Nerve System.
2.png#asset:852. Implication of nigrostriatal system in motor decline during aging
Chile has experienced sustained economic growth, leading to the highest income per capita in the region and our life expectancy is like USA. It is expected that by 2050, 23.5% of Chileans will be older than 60 years. For this reason, it is important to define the molecular mechanisms that underlie the aging process in order to improve the quality of life of the elderly population. Our laboratory belongs to Center for Geroscience, Brain Health and Metabolism (http://www.gerochile.org/es/home/), which is focus on preclinical and clinical aspects of specific cellular processes that represent central hallmarks for aging, such as, mitochondria dysfunction and metabolism, loss of proteostasis, inflammation, stem cell exhaustion and lack of regeneration. Our group is involved in to define the molecular components involved in the degeneration of the nigrostriatal system and its relationship with the decline of the motor capacity during the aging process.
3.png#asset:863. Biomarker studies in Parkinson and Huntington Chilean Patients
Currently, there is a growing need to know the genetic characteristics of our population, to define the incidence of genetic factors of neurodegenerative diseases. We to perform a characterization of biomarkers in patients of the Chilean population with Parkinson and Huntington Disease. We studied the presence of genetic alterations that have been previously described in these diseases, for example, the family of PARK genes in Parkinson Disease and the extension of the CAG repeat in the HTT gene in Huntington Disease, and its relationship with the decline of the motor capacity of the patients. These analyzes will be carried out from blood samples of patients who are in the early stages of the disease. This information will be used to monitor and treat patients. This research also aims to describe new biomarkers of these diseases in our country. Finally, we investigate the presence of specific biomarkers for the early diagnosis of these diseases

Name: FONDECYT REGULAR

Title: Neuronal exosomes characterization in Chilean Parkinson disease patients: Possible contribution of IGF2 in alpha-synuclein exosomal secretion

Funding Institution: CONOCYT

Responsible Researcher: Rene Vidal

Date of execution: 2019-2022

Nombre: FONDAP

Título: Geroscience Center for Brain Health and Metabolism

Co-Researcher: Rene Vidal

Funding Institution: CONICYT

Date of execution: 2016-2020

Name: Biomedical Neuroscience Institute (BNI).

Co-Researcher: Rene Vidal

Funding Institution: MINRED

Date of Execution: 2016-2020

Marisol Cisternas

Technical assistant

In charge of the studies of the GERO project. In this study, the mobility capacity of young and aged animals is compared. In addition, the growth factor is evaluated. IGF2 is able to prevent the motor deficit generated by the aging process.

Sirley Leal

Technical assistant

Investigates the role of IGF2 in Parkinson's disease in the framework of the FONDECYT project. This project has a series of cellular and animal models of the disease and the possible neuroprotective effect of IGF2 in this disease is being evaluated.

María José Hormazábal

PhD student

Makes her PhD thesis in Nutrition from the University of Chile. Investigates the effect of rapamycin and rapamycin analogues in preclinical models of Parkinson's disease and the possible metabolic effects of these drugs.

Alejandra Parra

PhD student

Makes her PhD thesis in Biomedical Sciences at the University of Chile. Evaluates the potential of spinal cord stimulation therapy in the treatment of Parkinson's disease and the molecular changes that underlie the long-term protective effect.

Paulina Troncoso

PhD student

Makes her PhD thesis in Biomedical Sciences at the University of Chile. Evaluates the effect of IGF2 on Huntington's disease using cellular and preclinical models of the disease.

Javiera Arcos

PhD student

Makes her PhD thesis in Neurobiology at the Universidad Mayor. Evaluates the effect of IGF2 on the secretion of alpha-synuclein and its therapeutic potential in Parkinson's disease.

International

Dr. Brian Kennedy, Buck Institute, California,USA - Scientific Collaboration

National

Dr. Claudio Hetz, Universidad de Chile - Scientific and Academic Collaboration

Dra. Soledad Matus, Fundación Ciencia y Vida - Scientific Collaboration

Dr. Oscar Cerda, Universidad de Chile - Scientific Collaboration

Dr. Rómulo Fuentes, Universidad de Chile - Scientific and Academic Collaboration

Dr. Roque Villagra, Hospital Salvador - Scientific Collaboration

Dr Carlos Aguilera, Hospital Fach - Scientific Collaboration

Dra. Brigitte Van Zundert, Universidad Andrés Bello - Scientific Collaboration

Dr. Pablo Moya, Universidad de Valparaíso - Academic Collaboration

Dr. Federico Batis, Universidad de Los Andes - Scientific Collaboration